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Control of luteinizing hormone-releasing hormone pulse generation in nonhuman primates

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Summary

1. The pulsatile release of luteinizing hormone-releasing hormone (LHRH) is critical for reproductive function. However, the exact mechanism of LHRH pulse generation is unclear. The purpose of this article is to review the current knowledge on LHRH pulse generation and to discuss a series of studies in our laboratory.

2. Using push-pull perfusion in the stalk-median eminence of the rhesus monkey several important facts have been revealed. There is evidence indicating that LHRH neurons themselves have endogenous pulse-generating mechanisms but that the pulsatility of LHRH release is also modulated by input from neuropeptide Y (NPY) and norepinephrine (NE) neurons. The release of NPY and NE is pulsatile, with their pulses preceding or occurring simultaneously with LHRH pulses, and the neuroligands NPY and NE and their agonists stimulate LHRH pulses, while the antagonists of the ligands suppress LHRH pulses.

3. The pulsatile release of LHRH increases during the estrogen-induced LH surge as well as the progesterone-induced LH surge. These increases are partly due to the stimulatory effects of estrogen and progesterone on NPY neurons.

4. An increase in pulsatile LHRH release occurs at the onset of puberty. This pubertal increase in LHRH release appears to be due to the removal of tonic inhibition from γ aminobutyric acid (GABA) neurons and a subsequent increase in the inputs of NPY and NE neurons to LHRH neurons.

5. There are indications that additional neuromodulators are involved in the control of the LHRH pulse generation and that glia may play a role in coordinating pulses of the release of LHRH and neuromodulators.

6. It is concluded that the mechanism generating LHRH pulses appears to comprise highly complex cellular elements in the hypothalamus. The study of neuronal and nonneuronal elements of LHRH pulse generation may serve as a model to study the oscillatory behavior of neurosecretion.

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References

  • Adelman, J. P., Mason, A. J., Hayflick, J. S., and Seeburg, P. H. (1986). Isolation of the gene and hypothalamic cDNA for the common precursor of gonadotropic-releasing hormone and prolactin release-inhibiting factor in human and rat.Proc. Natl. Acad. Sci. USA 83:179–183.

    PubMed  Google Scholar 

  • Andrew, R. D. (1989). Oscillatory activity in supraoptic nucleus. InNeuronal and Cellular Oscillators (J. W. Jacklet, Ed.), Dekker, New York, pp. 121–147.

    Google Scholar 

  • Andrew, R. D., and Dudek, F. E. (1983). Burst discharge in mammalian neuroendocrine cells involves an intrinsic regenerative mechanism.Science 221:1050–1052.

    PubMed  Google Scholar 

  • Backstrom, C. T., McNeilly, A. S., Leask, R. M., and Baird, D. T. (1982). Pulsatile secretion of LH, FSH, prolactin, oestradiol and progesterone during the human menstrual cycle.Clin. Endocrinol. (Oxf.) 17:29–42.

    Google Scholar 

  • Barker, J. L., and Smith, T. G., Jr. (1980). Bursting pacemaker activity in a peptidergic and peptide-sensitive neuron. InThe Role of Peptides in Neuronal Function (J. L. Baker, and T. G. Smith, Jr., Eds.), Dekker, New York, pp. 189–228.

    Google Scholar 

  • Barraclough, C. A., Wise, P. M., and Selmanoff, M. K. (1984). A role for hypothalamic catecholamines in the regulation of gonadotropin secretion.Rec. Prog. Horm. Res. 40:487–529.

    PubMed  Google Scholar 

  • Belchetz, P. E., Plant, T. M., Nakai, V., Keogh, E. J., and Knobil, E. (1978). Hypophyseal responses to continuous and intermittent delivery of hypothalamic gonadotropin-releasing hormone.Science 202:631–633.

    PubMed  Google Scholar 

  • Besecki, L. M., and Levine, J. E. (1994). Acute increase in responsiveness of luteinizing hormone (LH)-releasing hormone nerve terminals to neuropeptide-Y stimulation before the preovulatory LH surge.Endocrinology 135:63–66.

    PubMed  Google Scholar 

  • Bhattacharya, A. N., Dierschke, D. J., Yamaji, T., and Knobil, E. (1972). The pharmacologic blockade of the circhoral mode of LH secretion in ovariectomized rhesus monkeys.Endocrinology 90:778–786.

    PubMed  Google Scholar 

  • Blank, M. S., and Murphy, J. R. (1991). Luteinizing hormone sensitivity to naloxone in maturing male chimpanzees.Brain Res. Bull. 27:241–245.

    PubMed  Google Scholar 

  • Bourguignon, J. P., and Franchimont, P. (1984). Puberty-related increase in episodic LHRH release from rat hypothalamusin vitro.Endocrinology 114:1941–1943.

    PubMed  Google Scholar 

  • Burich, A. J., Claude, P., and Terasawa, E. (1994). LHRH neuronsin vitro derived from the embryonic olfactory placode of the rhesus monkey release LHRH into medium in a pulsatile manner.Proc. 24th Ann. Mtg. Soc. Neurosci. Abstr. 20:No. 272.4.

  • Byrnes, N. D., Cloutier, M. D., and Hayles, A. B. (1974). The central nervous system and precocious puberty. InThe Control of the Onset of Puberty (M. M. Grumbach, G. D. Grave, and F. E. Mayer, Eds.), Wiley and Sons, New York, pp. 213–237.

    Google Scholar 

  • Cameron, J. L., McNeill, T. J., Fraser, H. M., Bremmer, W. J., Clifton, D. K., and Steiner, R. A. (1985). The role of endogenous gonadotropin-releasing hormone neurons in the control of luteinizing hormone and testosterone secretion in the juvenile male monkey,Macaca fascicularis.Biol. Reprod. 33:147–156.

    PubMed  Google Scholar 

  • Caraty, A., Locatelli, A., and Martin, G. B. (1989). Biphasic response in the secretion of gonadotropin-releasing hormone in ovariectomized ewes injected with oestradiol.J. Endocrinol. 123:375–382.

    PubMed  Google Scholar 

  • Carmel, P. W., Araki, S., and Ferin, M. (1976). Pituitary stalk portal blood collection in rhesus monkeys: Evidence of pulsatile release of gonadotropin-releasing hormone (GnRH).Endocrinology 99:243–248.

    PubMed  Google Scholar 

  • Carraway, R., and Leeman, S. E. (1973). The isolation of a new hypotensive peptide, neurotensin from bovine hypothalamus.J. Biol. Chem. 248:6854–6861.

    PubMed  Google Scholar 

  • Chongthammakun, S., and Terasawa, E. (1991). Negative and positive feedback effects of estradiol on LHRH release occur in pubertal rhesus monkeys.Proc. 73rd Annu. Mtg. Endocr. Soc., p. 39 (No. 33).

  • Chongthammakun, S., and Terasawa, E. (1993). Negative feedback effects of estrogen on luteinizing hormone-releasing hormone release occur in pubertal, but not prepubertal, ovariectomized female rhesus monkeys.Endocrinology 132:735–743.

    PubMed  Google Scholar 

  • Chongthammakun, S., Claypool, L. E., and Terasawa, E. (1993). Ovariectomy increasesin vivo LHRH release in pubertal, but not prepubertal, female rhesus monkeys.J. Neuroendocrinol. 5:41–50.

    PubMed  Google Scholar 

  • Clarke, I. J. (1993). Variable patterns of gonadotropin-releasing hormone secretion during the estrogen-induced luteinizing hormone surge in ovariectomized ewes.Endocrinology 133:1624–1632.

    PubMed  Google Scholar 

  • Clarke, I. J., and Cummins, J. T. (1982). The temporal relationship between gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) secretion in the ovariectomized ewe.Endocrinology 111:1737–1739.

    PubMed  Google Scholar 

  • Clarke, I. J., and Cummins, J. T. (1985). Increased gonadotropin-releasing hormone pulse frequency associated with estrogen-induced luteinizing hormone surges in ovariectomized ewes.Endocrinology 116:2376–2383.

    PubMed  Google Scholar 

  • Clarke, I. J., Cummins, J. T., Karsch, F. J., Seeburg, P. H., and Nikolics, K. (1987). GnRH-associated peptide (GAP) is cosecreted with GnRH into the hypophyseal portal blood of ovariectomized sheep.Biochem. Biophys. Res. Comm. 143:665–671.

    PubMed  Google Scholar 

  • Claypool, L. E., and Terasawa, E. (1989). N-Methyl-D, L-aspartate (NMDA) induces LHRH release as measured byin vivo push-pull perfusion in the stalk-median eminence of pre-and peripubertal female rhesus monkeys.Biol. Reprod. (Suppl.)40:83 (No. 108).

    Google Scholar 

  • Claypool, L. E., Watanabe, G., and Terasawa, E. (1990). Effects of electrical stimulation of medial basal hypothalamus on thein vivo release of luteinizing hormone-releasing hormone in the prepubertal and peripubertal monkey.Endocrinology 127:3014–3022.

    PubMed  Google Scholar 

  • Cobbett, P., Inenga, K., and Mason, W. T. (1988). Mechanism of phasic bursting in vasopressin cells. InPulsatility in Neuroendocrine Systems (G. Leng, Ed.), CRC Press, Boca Raton, FL, pp. 155–179.

    Google Scholar 

  • Crowley, W. F., and Jameson, L. J. (1992). Gonadotropin-releasing hormone deficiency: Perspectives from clinical investigation.Endocr. Rev. 13:635–640.

    PubMed  Google Scholar 

  • Crowley, W. F., Jr., Filicori, M., Spratt, D. T., and Santoro, N. F. (1985). The physiology of gonadotropin-releasing hormone (GnRH) secretion in men and women.Rec. Prog. Horm. Res. 41:473–531.

    PubMed  Google Scholar 

  • Dierschke, D. J., Bhattacharya, A. N., Atkinson, L. E., and Knobil, E. (1970). Circhoral oscillations of plasma LH levels in the ovariectomized rhesus monkey.Endocrinology 87:850–853.

    PubMed  Google Scholar 

  • Dreifuss, J. J., Tribollet, E., Baertschi, A., and Lincoln, D. W. (1976). Mammalian endocrine neurons: Control of phasic activity of antidromic action potentials.Neurosci. Lett. 3:281–286.

    Google Scholar 

  • Ferin, M., van Vugt, D., and Wardlaw, S. (1984). The hypothalamic control of the menstrual cycle and the role of endogenous opioid peptides.Rec. Prog. Horm. Res. 40:441–485.

    PubMed  Google Scholar 

  • Filicori, M., Santro, N., Merriam, G. R., and Crowley, W. F., Jr. (1986). Characterization of the physiological pattern of episodic gonadotropin secretion throughout the human menstrual cycle.J. Clin. Endocrinol. Metab. 62:1136–1144.

    PubMed  Google Scholar 

  • Fox, S. R., Harlan, R. E., Shivers, B. D., and Pfaff, D. W. (1990). Chemical characterization of neuroendocrine targets for progesterone in the female rat brain and pituitary.Neuroendocrinology 51:276–283.

    PubMed  Google Scholar 

  • Gambacciani, M., Liu, J. H., Swartz, W. H., Tueros, V. S., Yen, S. C., and Rasmussen, D. O. (1987). Intrinsic pulsatility of luteinizing hormone release from the human pituitary in vitro.Neuroendocrinology 45:402–406.

    PubMed  Google Scholar 

  • Gay, V. L., and Plant, T. M. (1987). N-Methyl-DL-aspartate (NMDA) elicits hypothalamic GnRH release in prepubertal male rhesus monkeys (Macaca mulatta).Endocrinology 120:2289–2296.

    PubMed  Google Scholar 

  • Gay, V. L., and Sheth, N. A. (1972). Evidence for a periodic release of LH in castrated male and female rats.Endocrinology 90:158–162.

    PubMed  Google Scholar 

  • Gearing, M., and Terasawa, E. (1988). Luteinizing hormone releasing hormone (LHRH) neuroterminals mapped using the push-pull perfusion method in the rhesus monkey.Brain Res. Bull. 21:117–121.

    PubMed  Google Scholar 

  • Gearing, M., and Terasawa, E. (1991a). Theα 1-adrenergic neuronal system is involved in pulsatile release of luteinizing hormone-releasing hormone (LHRH) in the ovariectomized female monkey.Neuroendocrinology 93:373–381.

    Google Scholar 

  • Gearing, M., and Terasawa, E. (1991b). Suppression of luteinizing hormone (LH) release by theα 1-adrenergic receptor antagonist prazosin in the ovariectomized female rhesus monkey.Am. J. Primatol. 25:23–33.

    Google Scholar 

  • Gearing, M., and Terasawa, E. (1991c). Prostaglandin E2 mediates the stimulatory effect of methoxamine inin vivo luteinizing hormone-releasing hormone (LHRH) release in the ovariectomized female rhesus monkey.Brain Res. 560:276–281.

    PubMed  Google Scholar 

  • Goldsmith, P. C., Lamberts, R., and Brezina, L. R. (1983). Gonadotropin-releasing hormone neurons and pathways in the primate hypothalamus and forebrain. InAspects of Reproduction (R. L. Norman, Ed.), Academic Press, New York, pp. 7–45.

    Google Scholar 

  • Gore, A. C., and Terasawa, E. (1991). A role for norepinephrine in the control of the onset of puberty in female rhesus monkeys.Endocrinology 129:3009–3017.

    PubMed  Google Scholar 

  • Gore, A. C., Mitsushima, D., and Terasawa, E. (1993). A possible role of neuropeptide Y in the control of the onset of puberty in female rhesus monkeys.Neuroendocrinology 58:23–34.

    PubMed  Google Scholar 

  • Grumbach, M. M., and Kaplan, S. L. (1990). The neuroendocrinology of human puberty: An ontogenetic perspective. InControl of the Onset of Puberty (M. M. Grumbach, P. C. Sizonenko, and M. L. Aubert, Eds.), William & Wilkins, Baltimore, pp. 1–48.

    Google Scholar 

  • Hatton, G. I. (1985). Reversible synapse formation and modulation of cellular relationships in the adult hypothalamus under physiological conditions. InSynaptic Plasticity (C. W. Cotman, Ed.), Guilford Press, New York, pp. 373–404.

    Google Scholar 

  • Hoff, J. D., Quigley, M. E., and Yen, S. S. C. (1983). Hormonal dynamics at midcycle: A reevaluation.J. Clin. Endocrinol. Metab. 57: 792–796.

    PubMed  Google Scholar 

  • Hotchkiss, J., and Knobil, E. (1994). The menstrual cycle and its neuroendocrine control. InThe Physiology of Reproduction, 2nd ed. (E. Knobil, and J. D. Neill, Eds.), Raven Press, New York, pp. 711–749.

    Google Scholar 

  • Hutchison, J. S., Kubik, C. J., Nelson, P. B., and Zeleznik, A. J. (1987). Estrogen induces premature luteal regression in rhesus monkeys during spontaneous menstrual cycles, but not in cycles driven by exogenous gonadotropin-releasing hormone.Endocrinology 121:466–474.

    PubMed  Google Scholar 

  • Jensen, A. M., and Chiu, S. Y. (1990). Fluorescence measurement of changes in intracellular calcium induced by excitatory amino acids in cultured cortical astrocytes.J. Neurosci. 10:1165–1175.

    PubMed  Google Scholar 

  • Kalra, S. P. (1986). Neural circuitry involved in the control of LHRH secretion: A model for preovulatory LH release. InFrontiers in Neuroendocrinology (L. Martini, and W. R. Ganong, Eds.), Raven Press, New York, Vol. 9, pp. 31–75.

    Google Scholar 

  • Kalra, S. P. (1993). Mandatory neuropeptide-steroid signal for the preovulatory luteinizing hormone-releasing hormone discharge.Endocr. Rev. 14:507–538.

    PubMed  Google Scholar 

  • Kanagawa, K., and Matsuo, H. (1984). Purification and complete amino acid sequence ofα human atrial natriuretic polypeptide (α-hANP).Biochem. Biophys. Comm. 118:131–139.

    Google Scholar 

  • Kaufman, J.-M., Kesner, J. S., Wilson, R. C., and Knobil, E. (1985). Electrophysiological manifestation of luteinizing hormone-releasing hormone pulse generator activity in the rhesus monkey: influence ofα-adrenergic blocking agents.Endocrinology 116:1327–1333.

    PubMed  Google Scholar 

  • Kelly, M. J., Condon, T. P., Levine, J. E., and Ronnekleiv, O. K. (1985). Combined electrophysiological, immunocytochemical and peptide release measurements in the hypothalamic slice.Brain Res. 345:264–270.

    PubMed  Google Scholar 

  • Kesner, J. S., Wilson, R. C., Kaufman, J.-M., Hotchkiss, J., Chen, Y., Yamamoto, H., Pardo, R. R., and Knobil, E. (1987). Unexpected responses of the hypothalamic gonadotropin-releasing hormone “pulse generator” to physiological estradiol inputs in the absence of the ovary.Proc. Natl. Acad. Sci. USA 84:8745–8749.

    PubMed  Google Scholar 

  • Kimura, F., Nishihara, M., Hiruma, H., and Funabashi, T. (1991). Naloxone increases the frequency of the electrical activity of luteinizing hormone-releasing hormone pulse generator in long-term ovariectomized rats.Neuroendocrinology 53:97–105.

    PubMed  Google Scholar 

  • Kimura, F., Ito, E., Sano, A., Mizuno, T., Jinnai, K., and Hiruma, H. (1994). Effects of pentobarbital sodium on the preoptic noradrenaline release and LHRH pulse generator activity in the ovariectomized rat.Neuroendocrinology 60 (S1):50 (No. P2.34).

    PubMed  Google Scholar 

  • King, J. C., and Rubin, B. S. (1994). Dynamic changes in LHRH neurovascular terminals with various endocrine conditions in adults.Horm. Behav. 28:349–356.

    PubMed  Google Scholar 

  • King, J. C., Anthony, E. L. P., Fitzgerald, D. M., and Stopa, E. G. (1985). Luteinizing hormone-releasing hormone neurons in human preoptic/hypothalamus: Differential interneuronal location of immunoreactive forms.J. Clin. Endocrinol. Metab. 60:88–97.

    PubMed  Google Scholar 

  • Knobil, E. (1980). The neuroendrocine control of the menstrual cycle.Rec. Prog. Horm. Res. 36:53–88.

    PubMed  Google Scholar 

  • Kobayashi, H., Wada, M., and Uemura, H. (1972). The hypothalamic median eminence as a neuroendocrine organ.Med. J. Osaka Univ. 23:43–55.

    PubMed  Google Scholar 

  • Kokoris, G. J., Lam, N. Y., Ferin, M., Silverman, A.-J., and Gibson, M. J. (1988). Transplanted gonadotropin-releasing hormone neurons promote pulsatile luteinizing hormone secretion in congenitally hypogonadal (hyg) male mice.Neuroendocrinology 48:45–52.

    PubMed  Google Scholar 

  • Kozlowski, G. P., and Coats, P. W. (1985). Ependymoneuronal specializations between LHRH fibers and cells of the cerebroventricular system.Cell Tissue Res. 242:301–311.

    PubMed  Google Scholar 

  • Krey, L. C., Butler, W. R., and Knobil, E. (1987). Surgical disconnection of the medial basal hypothalamus and pituitary function in the rhesus monkey. I. Gonadotropin secretion.Endocrinology 96:1073–1087.

    Google Scholar 

  • Krsmanovic, L. Z., Stojilkovic, S. S., Merelli, F., Dufour, S. M., Virmani, M. A., and Catt, K. J. (1992). Calcium signaling and episodic secretion of gonadotropin-releasing hormone in hypothalamic neurons.Proc. Natl. Acad. Sci. USA 89:8462–8466.

    PubMed  Google Scholar 

  • Krsmanovic, L. Z., Stojilkovic, S. S., Mertz, L. M., Tomic, G., and Catt, K. J. (1993). Expression of gonadotropin-releasing hormone receptors and autocrine regulation of neuropeptide release in immortalized hypothalamic neurons.Proc. Natl. Acad. Sci. USA 90:3908–3912.

    PubMed  Google Scholar 

  • Krsmanovic, L. Z., Arora, K. K., Stojilkovic, S. S., and Catt, K. J. (1994). Autocrine regulation of gonadotropin-releasing hormone (GnRH) secretion via GnRH receptors expressed in cultured hypothalamic cells.Proc. Annu. Mtg. Endocr. Soc., p. 520 (No. 1280).

  • Levine, J. E., Pau, K. F., Ramirez, V. D., and Jackson, G. L. (1982). Simultaneous measurement of luteinizing hormone-releasing hormone and luteinizing hormone release in unanesthetized ovariectomized sheep.Endocrinology 111:1449–1455.

    PubMed  Google Scholar 

  • Levine, J. E., Norman, R. L., Gliessman, P. M., Oyama, T. T., Bangsberg, D. R., and Spies, H. G. (1985). In vivo gonadotropin-releasing hormone release and serum luteinizing hormone measurements in ovariectomized estrogen-treated rhesus macaques.Endocrinology 117:711–721.

    PubMed  Google Scholar 

  • Lincoln, D. W., and Wakerley, J. B. (1974). Electrophysiological evidence for the activation of supraoptic neurons during the release of oxytocin.J. Physiol. (London) 242:533–554.

    Google Scholar 

  • Llinás, R. R. (1988). The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function.Science 242:1654–1664.

    PubMed  Google Scholar 

  • Lundberg, J. M., Pernow, J., and Lacroix, J. S. (1989). Neuropeptide Y: Sympathetic cotransmitter and modulator?NIPS 4:13–17.

    Google Scholar 

  • Marder, E., and Hooper, S. L. (1989). Neurotransmitter modulation of the stomatogastric ganglion of decapod crustaceans. InModel Neural Networks and Behavior (A. I. Selverston, Ed.), Plenum, New York, pp. 319–337.

    Google Scholar 

  • Marshall, L. A., Monroe, S. E., and Jaffe, R. B. (1988). Physiologic and therapeutic aspects of GnRH and its analogs. InFrontiers in Neuroendocrinology (L. Martini, and W. F. Ganong, Eds.), Raven Press, New York, Vol. 10, pp. 239–278.

    Google Scholar 

  • Martinez de la Escalera, G., Choi, A. L. H., and Weiner, R. I. (1992). Generation and synchronization of gonadotropin-releasing hormone (GnRH) pulses: Intrinsic properties of the GT1-1 GnRH neuronal cell line.Proc. Natl. Acad. Sci. USA 89:1852–1855.

    PubMed  Google Scholar 

  • Matsumoto, A. M., Gross, K. M., and Bremmer, W. J. (1991). The physiological significance of pulsatile LHRH secretion in man: Gonadotropin responses to physiological doses of pulsatile verses continuous LHRH administration.Int. J. Androl. 14:23–32.

    PubMed  Google Scholar 

  • McDonald, J. K., Tigges, J., Tigges, M., and Reich, C. (1988). Developmental study of neuropeptide Y-like immunoreactivity in the neurohypophysis and intermediate lobe of the rhesus monkey (Macaca mulatta).Cell Tissue Res. 254:499–509.

    PubMed  Google Scholar 

  • McKibbin, P. E., and Belchetz, P. E. (1986). Prolonged pulsatile release of gonadotropin-releasing hormone from the guinea pig hypothalamusin vivo.Life Sci. 38:2145–2150.

    PubMed  Google Scholar 

  • Mellon, P. L., Windle, J. J., Goldsmith, P. C., Padula, C. A., Roberts, J. L., and Weiner, R. I. (1990). Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis.Neuron 5:1–10.

    PubMed  Google Scholar 

  • Mitsushima, D., Marzban, F., Hei, D. L., Golos, T. G., and Terasawa, E. (1993). Direct infusion of a glutamic acid decarboxylase (GAD1) antisense oligodeoxynucleotide into the stalk-median eminence (S-ME) increases thein vivo LHRH release in prepubertal female monkeys.Proc. 23rd Annu. Mtg. Soc. Neurosci. 19:618 (No. 58.1).

    Google Scholar 

  • Mitsushima, D., Hei, D. L., and Terasawa, E. (1994).γ-Aminobutyric acid is an inhibitory neurotransmitter restricting the release of luteinizing hormone-releasing hormone before the onset of puberty.Proc. Natl. Acad. Sci. USA 91:395–399.

    PubMed  Google Scholar 

  • Moenter, S. M., Caraty, A., and Karsh, F. J. (1990). The estradiol-induced surge of gonadotropin releasing hormone in the ewe.Endocrinology 127:1375–1384.

    PubMed  Google Scholar 

  • Moenter, S. M., Caraty, A., Locatelli, A., and Karsh, F. J. (1991). Pattern of GnRH secretion leading up to ovulation in the ewe: Existence of a preovulatory GnRH surge.Endocrinology 129:1175–1182.

    PubMed  Google Scholar 

  • Nishihara, M., Sano, A., and Kimura, F. (1994). Cessation of the electrical activity of gonadotropin-releasing hormone pulse generator during the steroid induced surge of luteinizing hormone in the rat.Neuroendocrinology 59:513–519.

    PubMed  Google Scholar 

  • O'Byrne, K. T., Thalabard, J.-C., Grosser, P. M., Wilson, R. C., Williams, C. L., Chen, M.-O., Ladendorf, D., Hotchkiss, J., and Knobil, E. (1991). Radiotelemetric monitoring of hypothalamic gonadotropin-releasing hormone pulse generator activity throughout the menstrual cycle of the rhesus monkey.Endocrinology 129:1207–1214.

    PubMed  Google Scholar 

  • Parpura, V., Basarsky, T. A., Liu, F., Jeftinija, K., Jeftinija, S., and Haydon, P. G. (1994). Glutamate-mediated astrocyte-neuron signaling.Nature 369:744–747.

    PubMed  Google Scholar 

  • Pau, K.-Y. F., Berria, M., Hess, D. L., and Spies, H. G. (1993). Preovulatory GnRH surge in ovarian intact rhesus macaques.Endocrinology 133:1650–1656.

    PubMed  Google Scholar 

  • Petraglia, F., Bernasconi, S., Inghetti, L., Loche, S., Romanini, F., Facchinetti, F., Marcellini, C., and Genazzani, A. R. (1986). Naloxone-induced luteinizing hormone secretion in normal, precocious, and delayed puberty.J. Clin. Endocrinol. Metab. 63:1112–1116.

    PubMed  Google Scholar 

  • Phelps, C. P., Kalra, S. P., and Kalra, P. S. (1990). The effect of prior surgical disconnection of the anterior mediobasal hypothalamus on LHRH release in vitro.Brain Res. 516:208–214.

    PubMed  Google Scholar 

  • Phillips, H. S., Nikolics, K., Branton, D., and Seeburg, P. H. (1985). Immunocytochemical localization in the rat brain of a prolactin release-inhibiting sequence of gonadotropin-releasing hormone.Nature 316:542–545.

    PubMed  Google Scholar 

  • Plant, T. M. (1985). A study of the role of the postnatal testes in determining the ontogeny of gonadotropin secretion in the male rhesus monkey (Macaca mulatta).Endocrinology 116:1341–1350.

    PubMed  Google Scholar 

  • Plant, T. M. (1988). Puberty in Primates. InThe Physiology of Reproduction (E. Knobil, and J. Neill, Eds.), Raven Press, New York, pp. 1763–1787.

    Google Scholar 

  • Plant, T. M., Nakai, Y., Belchetz, P., Keogh, E., and Knobil, E. (1978). The sites of action of estradiol and phentolamine in the inhibition of the pulsatile, circhoral discharges of LH in the rhesus monkey (Macaca mulatta).Endocrinology 102:1015–1018.

    PubMed  Google Scholar 

  • Plant, T. M., Gay, V. L., Marshall, G. R., and Arslan, M. (1989). Puberty in monkeys is triggered by chemical stimulation of the hypothalamus.Proc. Natl. Acad. Sci. USA 86:2506–2510.

    PubMed  Google Scholar 

  • Poulain, D. A., and Wakerley, J. B. (1982). Electrophysiology of hypothalamic magnocellular neurons secreting oxytocin and vasopressin.Neuroscience 7:773–808.

    PubMed  Google Scholar 

  • Pu, S., and Terasawa, E. (1993). Effects of neurotensin and atrial natriuretic peptide on thein vivo release of luteinizing hormone-releasing hormone in the stalk-median eminence in ovariectomized female rhesus monkeys.Proc. 23rd Annu. Mtg. Soc. Neurosci. 19:619 (No. 258.11).

    Google Scholar 

  • Pu, S., and Terasawa, E. (1994). Effects of an LHRH agonist analog infusion on the pulsatile release of LHRH and NPY in ovariectomized rhesus monkeys.Proc. 76th Annu. Mtg. Endocr. Soc., p. 521 (No. 1281).

  • Rabin, D., and McNeil, L. W. (1981). Pituitary and gonadal desensitization after continuous luteinizing hormone-releasing hormone infusion in normal females.J. Clin. Endocrinol. Metab. 51:873–876.

    Google Scholar 

  • Ramirez, V. D., Feder, H. H., and Sawyer, C.H. (1984). The role of brain catecholamines in the regulation of LH secretion: A critical inquiry. InFrontiers in Neuroendocrinology (W. F. Ganong, Ed.) Raven Press, New York, Vol. 7, pp. 27–84.

    Google Scholar 

  • Rasmussen, D. D., Gambacciani, M., Swartz, W., Tueros, V. S., and Yen, S. S. C. (1989). Pulsatile gonadotropin-releasing hormone release from the human mediobasal hypothalamusin vitro: Opiate receptor-mediated suppression.Neuroendocrinology 49:150–156.

    PubMed  Google Scholar 

  • Reame, N., Sander, S. E., Kelch, R. P., and Marshall, J. C. (1984). Pulsatile gonadotropin secretion during the human menstrual cycle: Evidence for altered frequency of gonadotropin-releasing hormone secretion.J. Clin. Endocrinol. Metab. 59:328–337.

    PubMed  Google Scholar 

  • Reiter, E. O., and Grumbach, M. M. (1982). Neuroendocrine control mechanisms and the onset of puberty.Annu. Rev. Physiol. 44:595–613.

    PubMed  Google Scholar 

  • Ronnekleiv, O. K., and Resko, J. A. (1990). Ontogeny of gonadotropin-releasing hormone-containing neurons in early fetal development of rhesus macaques.Endocrinology 126:498–511.

    PubMed  Google Scholar 

  • Rossmanith, W. G., Yen, S. S. C., and Rasmussen, D. D. (1990). Synchronous pulsatile release of luteinizing hormone and immunoreactive beta-endorphin from the human pituitaryin vitro.J. Neuroendocrinol. 2:91–94.

    Google Scholar 

  • Sar, M., Sahu, A., Crowley, W. R., and Kalra, S. P. (1990). Localization of neuropeptide-Y immunoreactivity in estradiol-concentrating cells in the hypothalamus.Endocrinology 127:2752–2756.

    PubMed  Google Scholar 

  • Sawyer, C. H. (1975). Some recent developments in brain-pituitary-ovarian physiology.Neuroendocrinology 17:97–124.

    PubMed  Google Scholar 

  • Shivers, B. D., Harlan, R. E., Morrell, J. I., and Pfaff, D. W. (1983). Absence of estradiol concentration in cell nuclei of LHRH-immunoreactive neurons.Nature 304:345–347.

    PubMed  Google Scholar 

  • Silverman, A.-J. (1988). The gonadotropin-releasing hormone (GnRH) neuronal systems: Immunocytochemistry. InThe Physiology of Reproduction (E. Knobil and J. Neill, Eds.), Raven Press, New York, pp. 1283–1304.

    Google Scholar 

  • Silverman, A. J., Antunes, J. L., Abrams, G. M., Nilaver, G., Thau, J. A., Robinson, J. A., Ferin, M., and Krey, L. C. (1982). The luteinizing hormone-releasing hormone pathways in rhesus (Macaca mulatta) and pigtailed (Macaca nemestrina) monkeys: New observations on thick, unembedded sections.J. Comp. Neurol. 211:309–316.

    PubMed  Google Scholar 

  • Silverman, A. J., Wilson, R. C., Kesner, J. S., and Knobil, E. (1986). Hypothalamic location of multiunit activity associated with pulsatile LH release in the rhesus monkey.Neuroendocrinology 44:168–171.

    PubMed  Google Scholar 

  • Smith, M. A., and Vale, W. W. (1981). Desensitization to gonadotropin-releasing hormone observed in superfused pituitary cells on cytodex beads.Endocrinology 108:752–759.

    PubMed  Google Scholar 

  • Southworth, M. B., Matsumoto, A. M., Gross, K. M., Soules, M. R., and Bremner, W. J. (1991). The importance of synal pattern in the transmission of endocrine information: Pituitary gonadotropin responses to continuous and pulsatile gonadotropin-releasing hormone.J. Clin. Endocrinol. Metab. 72:1286–1289.

    PubMed  Google Scholar 

  • Spratt, D. I., Carr, D. B., Merriam, G. R., Scully, R. E., Rao, P. N., and Crowley, W. F., Jr. (1987). The spectrum of abnormal pattern of gonadotropin-releasing hormone secretion in men and idiopathic hypogonadotropic hypogonadism: Clinical and laboratory correlations.J. Clin. Endocrinol. Metabl. 64:283–291.

    Google Scholar 

  • Tanaka, T., Mori, Y., and Hoshino, K. (1992). Hypothalamic GnRH pulse generator activity during the estradiol-induced LH surge in ovariectomized goats.Neuroendocrinology 56:641–645.

    PubMed  Google Scholar 

  • Terasawa, E. (1990). What is the LHRH pulse generator? A hypothesis. InPheromones and Reproduction (Y. Sagara and K. Seto, Eds.), Parthenon Pub. Group, Lancs, and Park Ridge, pp. 77–78.

    Google Scholar 

  • Terasawa, E. (1994). In vivo measurement of pulsatile release of neuropeptides and neurotransmitters in rhesus monkeys using push-pull perfusion. InMethods in Neuroscience: Pulsatility in Neuroendocrine System (J. E. Levine, Ed.), Academic Press, New York, pp. 184–202.

    Google Scholar 

  • Terasawa, E., and Chongthammakun, S. (1991). Developmental changes inin vivo release ofβ-endorphin (β-END) from the stalk-median eminence (S-ME) in female rhesus monkeys.Proc. 21st Annu. Mtg. Soc. Neurosci. 17:906 (No. 361.1).

    Google Scholar 

  • Terasawa, E., and Gore, A. C. (1992). Regulation of pulsatile LHRH release in primates. InModes of Action of GnRH and GnRH Analogs (W. F. Crowley, Jr., and P. M. Conn, Eds.), Springer-Verlag, New York, pp. 256–274.

    Google Scholar 

  • Terasawa, E., and Wiegand, S. J. (1978). Effects of hypothalamic deafferentation on ovulation and estrous cyclicity in the female guinea pig.Neuroendocrinology 26:229–248.

    PubMed  Google Scholar 

  • Terasawa, E., Rodriguez-Sierra, J. F., Dierschke, D. J., Bridson, W. E., and Goy, R. W. (1980). Positive feedback effect of progesterone on luteinizing hormone (LH) release in cyclic female rhesus monkeys: LH response occurs in two phases.J. Clin. Endocrinol. Metab. 51:1245–1250.

    PubMed  Google Scholar 

  • Terasawa, E., Noonan, J., and Bridson, W. E. (1982). Anesthesia with pentobarbitone blocks the progesterone-induced luteinizing hormone surge in the ovariectomized rhesus monkey.J. Endocrinol. 92:327–339.

    PubMed  Google Scholar 

  • Terasawa, E., Nass, T. E., Yeoman, R. R., Loose, M. D., and Schultz, N. J. (1983). Hypothalamic control of puberty. InNeuroendocrine Aspects of Reproduction (R. L. Norman, Ed.) (ORPRC Symposia on Primate Reproductive Biology), Academic Press, New York, pp. 149–182.

    Google Scholar 

  • Terasawa, E., Noonan, J. J., Nass, T. E., and Loose, M. D. (1984a). Posterior hypothalamic lesions advance the onset of puberty in the female rhesus monkey.Endocrinology 115:2241–2250.

    PubMed  Google Scholar 

  • Terasawa, E., Yeoman, R. R., and Schultz, N. J. (1984b). Factors influencing the progesterone-induced LH surge in rhesus monkeys: Diurnal influence and time interval after estrogen.Biol. Reprod. 31: 732–741.

    PubMed  Google Scholar 

  • Terasawa, E., Krook, C., Eman, S., Watanabe, G., Bridson, W. E., Sholl, S. A. and Hei, D. L. (1987). Pulsatile LH release during the progesterone-induced LH surge in the female rhesus monkey.Endocrinology 120:2265–2271.

    PubMed  Google Scholar 

  • Terasawa, E., Krook, C., Hei, D. L., Gearing, M., Schultz, N. J., and Davis, G. A. (1988). Norepinephrine is a possible neurotransmitter stimulating pulsatile release of luteinizing hormone releasing hormone in the rhesus monkey.Endocrinology 123:1808–1816.

    PubMed  Google Scholar 

  • Terasawa, E., Claypool, L., Watanabe, G., and Gore, A. (1989). The timing of the onset of puberty in the female rhesus monkey. InControl of the Onset of Puberty III. (H. A. Delemarre-Van de Waal, T. M. Plant, G. P. van Rees, and J. Shoemaker, Eds.), Elsevier, Amsterdam, pp. 123–136.

    Google Scholar 

  • Terasawa, E., Gore, A. C., and Saitoh, Y. (1992). Effects of adrenal medullary transplantation on the timing of puberty in the female rhesus monkey.Proc. 74th Annu. Mtg. Endocr. Soc., p. 332 (No. 1086).

  • Terasawa, E., Quanbeck, C. D., Schulz, C. A., Burich, A. J., Luchansky, L. L., and Claude, P. (1993). A primary cell culture system of luteinizing hormone releasing hormone (LHRH) neurons derived from fetal olfactory placode in the rhesus monkey.Endocrinology 133:2379–2390.

    PubMed  Google Scholar 

  • Turek, F. W., Swann, J., and Earnest, D. (1984). Role of the circadian system in reproductive phenomena.Rec. Prog. Horm. Res. 40:143–177.

    PubMed  Google Scholar 

  • Urbanski, H. F., and Ojeda, S. R. (1987). Activation of luteinizing hormone-releasing hormone release advances the onset of female puberty.Neuroendocrinology 46:273–275.

    PubMed  Google Scholar 

  • Urbanski, H. F., and Ojeda, S. R. (1990). A role for N-methyl-D-aspartate (NMDA) receptors in the control of LH secretion and initiation of female puberty.Endocrinology 126:1774–1776.

    PubMed  Google Scholar 

  • Vician, L., Adams, L. A., Clifton, O. K., and Steiner, R. A. (1991). Pubertal changes in proopiomelanocortin and gonadotropin-releasing hormone gene expression in the brain of the male monkey.Mol. Cell Neurosci. 2:31–38.

    Google Scholar 

  • Watanabe, G., and Terasawa, E. (1989).In vivo release of luteinizing hormone releasing hormone (LHRH) increases with puberty in the female rhesus monkey.Endocrinology 125:92–99.

    PubMed  Google Scholar 

  • Wetsel, W. C., Valenca, M. M., Merchenthaler, I., Lipositz, Z., Lopez, F. J., Weiner, R. I., Mellon, P. L., and Negro-Vilar, A. (1992). Intrinsic pulsatile secretory activity of immortalized luteinizing hormone-releasing hormone secreting neurons.Proc. Natl. Acad. Sci. USA 89:4149–4153.

    PubMed  Google Scholar 

  • Wildt, L., Marshall, G., and Knobil, E. (1980). Experimental induction of puberty in the infantile rhesus monkey.Science 207:1373–1375.

    PubMed  Google Scholar 

  • Wilson, R. C., Kesner, J. S., Kaufman, J.-M., Uemura, T., Akema, T., and Knobil, E. (1984). Central electrophysiological correlates of pulsatile luteinizing hormone secretion in the rhesus monkey.Neuroendocrinology 53:97–105.

    Google Scholar 

  • Winfree, A. T. (1967). Biological rhythms and the behavior of populations of coupled oscillators.J. Theoret. Biol. 16:15–42.

    Google Scholar 

  • Winter, J. S. D., and Faiman, C. (1972). Serum gonadotropin concentration in agonadal children and adults.J. Clin. Endocrinol. Metab. 35:561–564.

    PubMed  Google Scholar 

  • Woller, M. J., and Terasawa, E. (1991). Infusion of neuropeptide Y into the stalk-inedian eminence stimulates in vivo release of luteinizing hormone releasing hormone in gonadectomized rhesus monkeys.Endocrinology 128:1144–1150.

    PubMed  Google Scholar 

  • Woller, M. J., and Terasawa, E. (1993). Estradiol enhances the action of neuropeptide Y onin vivo luteinizing hormone-releasing hormone release in the ovariectomized female rhesus monkey.Neuroendocrinology 56:921–925.

    Google Scholar 

  • Woller, M. J., and Terasawa, E. (1994). Changes in pulsatile release of neuropeptide-Y and luteinizing hormone (LH)-releasing hormone during the progesterone-induced LH surge in rhesus monkeys.Endocrinology 135:1679–1686.

    PubMed  Google Scholar 

  • Woller, M. J., McDonald, J. K., Reboussin, D. M., and Terasawa, E. (1992). Neuropeptide Y is a neuromodulator of pulsatile LHRH release in the gonadectomized rhesus monkey.Endocrinology 430:2333–2342.

    Google Scholar 

  • Xia, L., Van Vugt, D., Alston, E. J., Luckhaus, J., and Ferin, M. (1992). A surge of gonadotropin-releasing hormone accompanies the estradiol-induced gonadotropin surge in the rhesus monkey.Endocrinology 131:2812–2820.

    PubMed  Google Scholar 

  • Yamane, A., and Terasawa, E. (1992). Pulsatile LHRH release is independently controlled by the alpha-adrenergic and neuropeptide Y neuronal systems in the rhesus monkey.Proc. 22nd Annu. Mtg. Soc. Neurosci. 18:192 (No. 90.6).

    Google Scholar 

  • Yen, S. S. C. (1980). Neuroendocrine regulation of the menstrual cycle. InNeuroendocrinology: A Hospital Practice Book (D. T. Krieger, and J. C. Hughes, Eds.), Sinauer Associates, Sunderland, MA, pp. 259–272.

    Google Scholar 

  • Yeoman, R. R., and Terasawa, E. (1984). An increase in single unit activity of the medial basal hypothalamus occurs during the progesterone-induced LH surge in the female rhesus monkey.Endocrinology 115:2445–2453.

    PubMed  Google Scholar 

  • Yeoman, R. R., Norman, R. L., and Terasawa, E. (1984). Medial basal hypothalamus lesions (MBHL) and pituitary stalk section (SS) block the progesterone-induced LH surge in ovariectomized rhesus monkeys.Proc. Int. Congr. Endocrinol., Abstr. No. 2071.

  • Zhang, S. J., and Jackson, M. B. (1993). GABA-activated chloride channels in secretory nerve endings.Science 259:531–534.

    PubMed  Google Scholar 

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Terasawa, E. Control of luteinizing hormone-releasing hormone pulse generation in nonhuman primates. Cell Mol Neurobiol 15, 141–164 (1995). https://doi.org/10.1007/BF02069563

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