Abstract
In this study, quantitative assessment of the synergistic and independent effects of estradiol and progesterone on protein synthesis in the ventromedial hypothalamus (VMN) and the preoptic area (POA) was accomplished usingin vitro 35S-methionine and35S-cystein labeling, two-dimensional gel electrophoresis, and computerized densitometry. Ovariectomized (OVX) rats were divided into four groups. Group 1 was implanted with estradiol (E) capsules for 6 hr and injected with progesterone (P; 0.1 ml, 5 mg/ml propylene glycol) at 20 hr. Group 3 was sham-implanted for 6 hr and injected with 0.01 ml P at 20 hr. Group 4 was sham-planted for 6 hr and injected with vehicle alone at 20 hr. All animals were sacrificed at 24 hr. A number of proteins in both VMN and POA were found to be increased or decreased in labeling by E plus P, E alone, and P alone. Two important synergistic effects of the hormones were found. First, the effects of E on labeling of several proteins in both brain regions were countered by P, and conversely, the effects of P on labeling of several proteins in both brain regions were countered by E. Second, E priming increased the number of proteins affected in labeling by P in both brain regions. Comparison of the effects of E and P on proteins in the VMN and POA indicated that the populations of proteins affected in labeling were markedly different. These results begin to clarify the mechanism in which E and P affect neuronal functioning in two regions involved in the control of reproduction and lend support to the hypothesis that gonadal steroids accomplished their action on brain tissue via a mechanism that is partly unique to the brain region.
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Barfield, R. J., and Chen, J. J. (1977). Activation of estrous behavior in ovariectomized rats by intracerebral implants of estradiol benzoate.Endocrinology 101: 1716–1725.
Brown, J. J., Moore, M. J., and Blaustein, J. D. (1987). Maintenance of progesterone-facilitated sexual behavior in the female rat requires continued hypothalamic protein synthesis and nuclear progestin receptor occupation.Endocrinology 121: 298–304.
Cohen, R., and Pfaff, D. W. (1981). Ultrastructure of neurons in the ventromedial nucleus of the hypothalamus in ovariectomized rats with or without estrogen treatment.Cell Tissue Res. 217: 451–470.
Jensen, E. V., Greene, G. L., Closs, L. E., DeSombre, E. R., and Nadji, M. (1982). Receptors reconsidered: A 20-year perspective.Recent Prog. Horm. Res. 38: 1–40.
Jones, K. J., Pfaff, D. W., and McEwen, B. S. (1985). Early estrogen-induced nuclear changes in rat hypothalamic ventromedial neurons: An ultrastructural and morphometric analysis.J. Comp. Neurol. 239: 255–266.
Jones, K. J., Chikaraishi, D. M., Harrington, C. A., McEwan, B. S., and Pfaff, D. W. (1986a).In situ hybridization detection of estradiol-induced changes in ribosomal RNA levels in rat brain.Mol. Brain Res. 1: 45–52.
Jones, K. J., McEwen, B. S., and Pfaff, D. W. (1986b). Regional specificity in estradiol effects of3Huridine incorporation in rat brain.Mol. Cell. Endrocrinol. 45: 57–63.
Krey, L. C., and Parsons, B. (1982). Characterization of the estrogen stimulus sufficient to restore cyclic luteinizing hormone release in recently ovariectomized rats.Neuroendocrinology 34: 315–322.
Legan, S. J., Coon, G. A., and Karsch, F. J. (1975). Role of estrogen as initiator of daily LH surges in the ovariectomized rat.Endocrinology 96: 50.
McEwan, B. S., Jones, K. J., and Pfaff, D. W. (1987). Hormonal control of sexual behavior in the female rat: Molecular, cellular and neurochemical studies.Biol Reprod. 36: 37–45.
Meisel, R., and Pfaff, D. W. (1985). Brain region specificity in estradiol effects on neuronal ultrastructure in rats.Mol Cell. Endocrinol. 40: 159–166.
Mileusnic, R., Kanazir, S., Ruzdijic, S., and Rakic, L. (1985). Effects of cortisol treatment on protein synthesis in septum and hippocampus of rat brain.Neuroendocrinology 42: 306–310.
Morrell, J., and Pfaff, D. W. (1978). A neuroendocrine approach to brain function: Localization of sex steroid concentrating cells in vertebrate brains.Am. Zool. 18: 447–460.
O'Farrell, P. H. (1975). High resolution two-dimensional electrophoresis of proteins.J. Biol. Chem. 250: 4007–4021.
O'Malley, B. W., and Means, A. R. (1974). Female steroid hormones and target cell nuclei.Science 183: 610–620.
Palkovits, M. (1980).Guide and Map for the Isolated Removal of Individual Cell Groups from the Rat Brain, Akademiai Kiado, Budapest.
Parsons, B., McEwen, B. S., and Pfaff, D. W. (1982a). A discontinuous schedule of estradiol treatment is sufficient to activate progesterone-facilitated feminine sexual behavior and to increase cytosol receptors for progestins in the hypothalamus of the rat.Endocrinology 110: 613–619.
Parsons, B., Rainbow, T. C., Pfaff, D. W., and McEwen, B. S. (1982b). Hypothalamic protein synthesis essential for the activation of the lordosis reflex in the female rat.Endocrinology 110: 620–624.
Pfaff, D. W. (1980).Estrogens and Brain Function. Neural Analysis of a Hormone-Controlled Mammalian Reproductive Behavior, Springer-Verlag, New York.
Pfaff, D. W., and Keiner, M. (1973). Atlas of estradiol-concentrating cells in the central nervous system of the female rat.J. Comp. Neurol. 151: 121–158.
Rainbow, T. C., Davies, P. G., and McEwen, B. S. (1980). Amisomycin inhibits the activation of sexual behavior by estradiol and progesterone.Brain Res. 194: 548–555.
Rainbow, T. C., McGinnis, M., Davis, P., and McEwen, B. S. (1982). Application of anisomycin to the lateral ventromedial nucleus of the hypothalamus inhibits the activation of sexual behavior by estradiol and progesterone.Brain Res. 223: 417–423.
Rodriguez-Sierra, J. F., Heydorn, W. E., Creed, G. J., and Jacobowitz, D. M. (1986). Isolation of specific proteins affected by estradiol in the arcuate-median eminence of prepuberal female rats.Brain Res. 399: 379–382.
Scouten, C., Heydorn, W., Creed, G., Malsbury, C., and Jacobowitz, D. (1985). Proteins regulated by gonadal steroids in the medial preoptic and ventromedial hypothalamic nuclei of male and female rats.Neuroendocrinology 41: 237–245.
Spelsberg, T. C., Littlefield, B. A., Seelke, R., Dani, G. M., Toyoda, H., Boyd-Leinen, P., Thrall, C., and Kon, O. L. (1983). Role of specific chromosomal proteins and DNA sequences in the nuclear binding sites for steroid receptors.Recent. Prog. Horm. Res. 39: 463–517.
Stanley, H. F., and Fink, G. (1985). The short-term effects of testosterone on brain protein synthesis in 4 day old rats: An electrophoretic study of proteins following intraventricular injection of35S-methionine.Brain Res. 358: 241–248.
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Jones, K.J., McEwen, B.S. & Pfaff, D.W. Quantitative assessment of the synergistic and independent effects of estradiol and progesterone on ventromedial hypothalamic and preoptic-area proteins in female rat brain. Metab Brain Dis 2, 271–281 (1987). https://doi.org/10.1007/BF00999697
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DOI: https://doi.org/10.1007/BF00999697