Skip to main content
SpringerLink
Log in

Luteolysins and Mechanisms of Luteolysis

  • Chapter
The Primate Ovary

Part of the book series: Serono Symposia, USA ((SERONOSYMP))

  • 77 Accesses

Abstract

A fundamentally important event in reproduction is luteolysis because without a decrease in progesterone secretion, there can be no gonadotropin-dependent ovarian differentiation and cyclic function. Until the last two decades, virtually nothing was known of the mechanisms of luteolysis or of the agents that regulate such processes. It was the pioneering work of researchers at the Upjohn Company which led to the finding that prostaglandin (PG) F2α was luteolytic in the laboratory rat (1). This eicosanoid produces luteal regression in a host of domestic and laboratory animals. PGF2α is generally regarded to be the major physiological uterine luteolysin in domestic species (2), but PGF2α is not an effective luteolysin in women. Thus, in the human, progress in understanding the mechanisms of luteolysis has not been as rapid. Nevertheless, from studies using ovarian cells from diverse species, an understanding of the nature of luteolysins and the mechanisms of luteolysis in the human may ultimately be realized.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 16.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Pharriss BB, Wyngarden LJ. The effect of prostaglandin F2α on the progestagen content of ovaries from pseudopregnant rats. Proc Soc Exp Biol Med 1969; 130:92–4.

    PubMed  CAS  Google Scholar 

  2. Thatcher WW, Bazer FW, Sharp DC, Roberts RM. Interrelationships between uterus and conceptus to maintain corpus luteum function in early pregnancy: sheep, cattle, pigs, and horses. J Anim Sci 1986; 62(suppl 2):25–46.

    PubMed  Google Scholar 

  3. Horton EW, Poyser NI. Uterine luteolytic hormone: a physiological role for prostaglandin F2α. Physiol Rev 1976; 56:595–651.

    PubMed  CAS  Google Scholar 

  4. Neill JD, Johansson ED, Knobil E. Failure of hysterectomy to influence the normal pattern of cyclic progesterone secretion in the rhesus monkey. Endocrinology 1969; 84:464–7.

    Article  PubMed  CAS  Google Scholar 

  5. Wiltbank JN, Ingalls JE, Rowden WW. Effects of various forms and levels of estrogens alone and in combinations with gonadotrophins on the estrous cycle of beef heifers. J Anim Sci 1961; 20:341–6.

    CAS  Google Scholar 

  6. Fogwell RL, Cowley JA, Wortman JA, Ames NK, Ireland JJ. Luteal function in cows following destruction of ovarian follicles at midcycle. Theriogenology 1985; 23:389–98.

    Article  PubMed  CAS  Google Scholar 

  7. Armstrong DT, Hansel W. Alteration of the bovine estrous cycle with oxytocin. J Dairy Sci 1959; 42:533–42.

    Article  Google Scholar 

  8. Flint APF, Sheldrick EL, Theodosis DT, Wooding FBP. Ovarian peptides: role of luteal oxytocin in the control of estrous cyclicity in ruminants. J Anim Sci 1986; 62(suppl 2):62–71.

    PubMed  Google Scholar 

  9. Soloff MS. Regulation of oxytocin action at the receptor level. In: Bottari S, Thomas JP, Vokaer A, Vokaer R, eds. Uterine contractility. New York: Mason Publishing, 1982:261–4.

    Google Scholar 

  10. Roberts JS, McCracken JA, Gavagan JE, Soloff MS. Oxytocin-stimulated release of prostaglandin F2α from ovine endometrium in vitro: correlation with estrous cycle and oxytocin-receptor binding. Endocrinology 1976; 99:1107–14.

    Article  PubMed  CAS  Google Scholar 

  11. Flint APF, Sheldrick EL. Ovarian secretion of oxytocin is stimulated by prostaglandin. Nature 1982; 297:587–8.

    Article  PubMed  CAS  Google Scholar 

  12. Rogers RJ, O’Shea JD, Findlay JK, Flint APF, Sheldrick EL. Large luteal cells the source of oxytocin in the sheep. Endocrinology 1983; 113:2302–4.

    Article  Google Scholar 

  13. Thorburn GD, Cox RI, Currie WB, Restall BJ, Schneider W. PGF2α and progesterone concentration in utero-ovarian venous plasma of the ewe during the estrous cycle and pregnancy. J Reprod Fertil 1973; (suppl 18):151–8.

    Google Scholar 

  14. Hirst JJ, Rice GE, Jenkin G, Thorburn GD. Secretion of oxytocin and progesterone by ovine corpora lutea in vitro. Biol Reprod 1986; 35:1106–14.

    Article  PubMed  CAS  Google Scholar 

  15. Tan GJS, Tweedale R, Biggs JSG. Effects of oxytocin on the bovine corpus luteum of early pregnancy. J Reprod Fertil 1982; 66:75–8.

    Article  PubMed  CAS  Google Scholar 

  16. Tan GJS, Tweedale R, Biggs JSG. Oxytocin may play a role in the control of the human corpus luteum. J Endocrinol 1982; 95:65–70.

    Article  PubMed  CAS  Google Scholar 

  17. Behrman HR, Macdonald GJ, Greep RO. Regulation of ovarian cholesterol esters: evidence for the enzymatic sites of prostaglandininduced loss of corpus luteum function. Lipids 1971; 6:791–6.

    Article  PubMed  CAS  Google Scholar 

  18. Behrman HR, Grinwich DL, Hichens M, Macdonald GJ. Effect of hypophysectomy, prolactin and PGF2α on LH and prolactin binding in vivo and in vitro in the corpus luteum. Endocrinology 1978; 103:349–57.

    Article  PubMed  CAS  Google Scholar 

  19. Pang CY, Behrman HR. Acute effects of PGF2α on ovarian and luteal blood flow, luteal gonadotropin uptake in vivo and gonadotropin binding in vitro. Endocrinology 1981; 108:2239–44.

    Article  PubMed  CAS  Google Scholar 

  20. Behrman HR, Ng TS, Orzcyk GP. Interactions between prostaglandins and gonadotropins in corpus luteum function. In: Moudgal NR, ed. Gonadotropins and gonadal function. New York: Academic Press, 1974:332–44.

    Google Scholar 

  21. Thomas JP, Dorflinger LJ, Behrman HR. Mechanism of the rapid antigonadotropic action of prostaglandins in cultured luteal cells. Proc Natl Acad Sci USA 1978; 75:1344–8.

    Article  PubMed  CAS  Google Scholar 

  22. Hichens M, Grinwich DL, Behrman HR. PGF2α -induced loss of corpus luteum receptors. Prostaglandins 1984; 7:449.

    Google Scholar 

  23. Grinwich DL, Hichens M, Behrman HR. Control of the LH receptor by prolactin and PGF2α in rat corpora lutea. Biol Reprod 1976; 14:212–8.

    Article  PubMed  CAS  Google Scholar 

  24. Behrman HR, Hichens M. Rapid block of gonadotropin uptake by corpora lutea in vivo induced by PGF2α. Prostaglandins 1976; 12:83–95.

    Article  PubMed  CAS  Google Scholar 

  25. Dorflinger LJ, Albert PJ, Williams AT, Behrman HR. Calcium is an inhibitor of LH-sensitive adenylate cyclase in the luteal cell. Endocrinology 1984; 114:1208–15.

    Article  PubMed  CAS  Google Scholar 

  26. Dorflinger LJ, Luborsky JL, Gore SD, Behrman HR. Inhibitory characteristics of PGF2α in the rat luteal cell. Mol Cell Endocrinol 1983; 33:225–41.

    Article  PubMed  CAS  Google Scholar 

  27. Wright K, Pang CY, Behrman HR. Luteal membrane binding of PGF2α and sensitivity of corpora lutea to PGF2α -induced luteolysis in pseudopregnant rats. Endocrinology 1980; 106:1333–7.

    Article  PubMed  CAS  Google Scholar 

  28. Luborsky JL, Behrman HR. LH receptor antiserum interacts with LH receptors but does not change hormone binding. Biochem Biophys Res Commun 1979; 90:1407–13.

    Article  PubMed  CAS  Google Scholar 

  29. Luborsky JL, Dorflinger LJ, Wright K, Behrman HR. PGF2α inhibits LH-induced increase in LH receptor binding to isolated rat luteal cells. Endocrinology 1984; 115:2210–6.

    Article  PubMed  CAS  Google Scholar 

  30. Luborsky JL, Slater WT, Behrman HR. LH receptor aggregation: modification of ferritin-LH binding and aggregation by PGF2α and ferritin LH. Endocrinology 1984; 115:2217–26.

    Article  PubMed  CAS  Google Scholar 

  31. Luborsky JL. Molecular interactions and cell surface receptor rearrangement in response to LH binding [Abstract]. 67th Meeting Endocrine Society, 1985:226.

    Google Scholar 

  32. Carlson JC, Buhr MM, Gruber MY, Thompson JE. Compositional and physical properties of microsomal membrane lipids from regressing rat corpora lutea. Endocrinology 1981; 108:2124–8.

    Article  PubMed  CAS  Google Scholar 

  33. Gore SD, Behrman HR. Alteration of transmembrane sodium and potassium gradients inhibits the action of LH in the luteal cell. Endocrinology 1984; 114:2020–31.

    Article  PubMed  CAS  Google Scholar 

  34. Verma AK, Penniston JT. A high affinity calcium-stimulated and magnesium-dependent ATPase in rat corpus luteum plasma membrane fractions. J Biol Chem 1981; 256:1269–75.

    PubMed  CAS  Google Scholar 

  35. Albert PJ, Preston SL, Behrman HR. Prostaglandin-induced luteolysis linked to inhibition of calcium pump activity [Abstract]. 7th International Congress of Endocrinology 1984:340.

    Google Scholar 

  36. Burgess GM, Godfrey PP, McKinney JS, Berridge MJ, Irvine RF, Putney JW. The second messenger linking receptor activation to internal calcium release in liver. Nature 1984; 309:63–6.

    Article  PubMed  CAS  Google Scholar 

  37. Raymond V, Leung PCK, Labrie F. Stimulation by PGF2α of phosphatidic acid-phosphatidyl inositol turnover in rat luteal cells. Biochem Biophys Res Commun 1983; 116:39–46.

    Article  PubMed  CAS  Google Scholar 

  38. Leung PCK, Minegishi T, Ma F, Zhou F, Ho-Yuen B. Induction of polyphosphoinositide breakdown in rat corpus luteum by prostaglandin F2α. Endocrinology 1986; 119:12–8.

    Article  PubMed  CAS  Google Scholar 

  39. Davis JS, Weakland LL, Weiland DA, Farese RV, West LA. Prostaglandin F2α stimulates phosphatidylinositol 4,5-bisphosphate hydrolysis and mobilizes intracellular Ca2+ in bovine luteal cells. Proc Natl Acad Sci USA 1987; 84:3728–32.

    Article  PubMed  CAS  Google Scholar 

  40. Behrman HR, Albert PJ, Preston SL. Calcium-inhibition of luteal adenylate cyclase is blocked by GTP. Biol Reprod 1984; 30(suppl 1): 58.

    Google Scholar 

  41. Takai Y, Kishimoto A, Kikkawa U, Mori T, Nishizuka Y. Unsaturated diacylglycerol as a possible messenger for the activation of calciumactivated, phospholipid-dependent protein kinase system. Biochem Biophys Res Commun 1979; 91:1218–24.

    Article  PubMed  CAS  Google Scholar 

  42. Davis JS, Clark MR. Activation of protein kinase in the bovine corpus luteum by phospholipid and Ca2α. Biochem J 1983; 214:569–74.

    PubMed  CAS  Google Scholar 

  43. Veldhuis JD, Demers LM. An inhibitory role for the protein kinase C pathway in ovarian steroidogenesis. Biochem J 1986; 239:505–11.

    PubMed  CAS  Google Scholar 

  44. Van Duuren BL, Sivak A. Tumor-promoting agents from croton tiglium L and their mode of action. Cancer Res 1968; 28:2349–56.

    PubMed  Google Scholar 

  45. Sender Baum M, Rosberg S. A phorbol ester, phorbol 12-myristate 13-acetate, and a calcium ionophore, A23187, can mimic the luteolytic effect of prostaglandin F2α in isolated luteal cells. Endocrinology 1987; 120:1019–26.

    Article  Google Scholar 

  46. Vande Wiele RL, Bogumil J, Dyrenfurth I, et al. Mechanisms regulating the menstrual cycle in women. Recent Prog Horm Res 1970; 26:63.

    Google Scholar 

  47. Yen SSC, Tsai CC, Naftolin F, Vandenberg G, Ajabor L. Pulsatile patterns of gonadotropin release in subjects with and ovarian function. J Clin Endocrinol Metab 1972; 34:671–5.

    Article  PubMed  CAS  Google Scholar 

  48. Reame N, Sauder SE, Kelch RP, Marshall JC. Pulsatile gonadotropin secretion during the human menstrual cycle: evidence for altered frequency of gonadotropin-releasing hormone secretion. J Clin Endocrinol Metab 1984; 59:328–37.

    Article  PubMed  CAS  Google Scholar 

  49. Hutchison JS, Nelson PB, Zeleznik AJ. Effects of different pulse frequencies on corpus luteum function during the menstrual cycle of rhesus monkeys. Endocrinology 1986; 119:1964–71.

    Article  PubMed  CAS  Google Scholar 

  50. Eyster KM, Ottobre JS, Stouffer RL. Adenylate cyclase in the corpus luteum of the rhesus monkey. III. Changes in basal and gonadotropin-sensitive activities during the luteal phase of the menstrual cycle. Endocrinology 1985; 117:1571–7.

    Article  PubMed  CAS  Google Scholar 

  51. Schaeffer JM, Liu J, Hsueh AJW. Presence of oxytocin and argininevasopressin in human ovary, oviduct and follicular fluid. J Clin Endocrinol Metab 1984; 59:970–3.

    Article  PubMed  CAS  Google Scholar 

  52. Auletta FJ, Paradis DK, Wesley M, Duby RT. Oxytocin is luteolytic in the rhesus money (Macaca mulatta). J Reprod Fertil 1984; 72:401–6.

    Article  PubMed  CAS  Google Scholar 

  53. Challis JRG, Calder AA, Dilley S, et al. Production of prostaglandins E and F by corpora lutea, corpora albicantes and stroma of the human ovary. J Endocrinol 1976; 68:401–8.

    Article  PubMed  CAS  Google Scholar 

  54. Powell WS, Hammerstrom S, Samuelsson B, Sjoberg B. Prostaglandin F2α receptor in human corpora lutea. Lancet 1974; 1:1120.

    Article  PubMed  CAS  Google Scholar 

  55. Dennefors B, Sjoren A, Hamberger L. Progesterone and 3′,5′-monophosphate formation by isolated human corpora lutea of different ages. Influence of human chorionic gonadotropin and prostaglandins. J Clin Endocrinol Metab 1982; 55:102–7.

    Article  PubMed  CAS  Google Scholar 

  56. Korda AR, Shutt DA, Smith ID, Shearman RP, Lyneham RC. Assessment of possible luteolytic effect of intraovarian injection of prostaglandin F2α in the human. Prostaglandins 1975; 9:443–9.

    Article  PubMed  CAS  Google Scholar 

  57. Auletta FJ, Speroff L, Caldwell BV. Prostaglandin F2α induced steroidogenesis and luteolysis in the primate corpus luteum. J Clin Endocrinol Metab 1973; 36:405–7.

    Article  PubMed  CAS  Google Scholar 

  58. Auletta FJ, Caldwell BV, Speroff L. Estrogen-induced luteolysis in the rhesus monkey: reversal with Indomethacin. Prostaglandins 1976; 11:745–52.

    Article  PubMed  CAS  Google Scholar 

  59. Gibson M, Auletta FJ. Effect of prostaglandin synthesis inhibition on human corpus luteum function. Prostaglandins 1986; 31:1023–8.

    Article  PubMed  CAS  Google Scholar 

  60. Karsch FJ, Sutton GP. An intraovarian site for the luteolytic action of estrogen in the rhesus monkey. Endocrinology 1976; 98:553–61.

    Article  PubMed  CAS  Google Scholar 

  61. Butler WR, Hochkiss J, Knobil E. Functional luteolysis in the rhesus monkey: ovarian estrogen and progesterone during the luteal phase of the menstrual cycle. Endocrinology 1975; 96:1509–12.

    Article  PubMed  CAS  Google Scholar 

  62. Aten RF, Williams AT, Behrman HR. Ovarian gonadotropin-releasing hormone-like protein (s): demonstration and characterization. Endocrinology 1986; 118:961–7.

    Article  PubMed  CAS  Google Scholar 

  63. Aten RF, Ireland JJ, Weems CW, Behrman HR. Presence of gonadotropin-releasing hormone-like proteins in bovine and ovine ovaries. Endocrinology 1987; 120:1727–33.

    Article  PubMed  CAS  Google Scholar 

  64. Aten RF, Ireland JJ, Behrman HR. The ovarian GnRH-like protein is antigonadotropic in both rat luteal and granulosa cells [Abstract]. 69th Annual Meeting of the Endocrine Society, Indianapolis, IN, 1987.

    Google Scholar 

  65. Aten RF, Polan ML, Bayless R, Behrman HR. A gonadotropin-releasing hormone (GnRH)-like protein in human ovaries: similarity to the GnRH-like protein of the rat. J Clin Endocrinol Metab 1987; 64:1288–93.

    Article  PubMed  CAS  Google Scholar 

  66. Ireland JJ, Aten RF, Behrman HR. Selective localization of the antigonadotropic GnRH-like protein in corpora lutea of the bovine ovary [Abstract]. Biol Reprod 1987; 36(suppl 1).

    Google Scholar 

  67. Clayton RN, Harwood JP, Catt KJ. Gonadotropin-releasing hormone analog binds to luteal cells and inhibits progesterone production. Nature 1979; 282:90–2.

    Article  PubMed  CAS  Google Scholar 

  68. Behrman HR, Preston SL, Hall AH. Cellular mechanism of the antigonadotropic action of luteinizing hormone-releasing hormone in the corpus luteum. Endocrinology 1980; 107:656–64.

    Article  PubMed  CAS  Google Scholar 

  69. Iwanov PP, Mescherskaya KA. Die physiologischen besonderheiten der geschlechtlich unreifen insecktenovarien und die zyklischen Veranderungen ihrer eigenschaften. Zool Jb (Physiol) 1935; 55:281–8.

    Google Scholar 

  70. Borovsky D. Isolation and characterization of highly purified mosquito oostatic hormone. Arch Insect Biochem Physiol 1985; 2:333–49.

    Article  CAS  Google Scholar 

  71. Hochachka PW. Defense strategies against hypoxia and hypothermia. Science 1986; 231:234–41.

    Article  PubMed  CAS  Google Scholar 

  72. Behrman HR, Aten RF, Luborsky JL, Polan ML, Miller JGO, Soodak LK. Purines, prostaglandins and peptides: nature and mechanisms of local assist and assassin agents in the ovary. J Anim Sci 1986; 62(suppl 2):14–24.

    PubMed  Google Scholar 

  73. Soodak LK, Macdonald GJ, Behrman HR. LH—a regulator of adenosine release in the rat corpus luteum. Biol Reprod 1986; 34(suppl 1).

    Google Scholar 

  74. Cross JC, Soodak LK, Musicki B, Behrman HR. Absence of detectable phosphocreatine in rat luteal cells. Am J Physiol 1987 (in press).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Reproductive Biology Section, Departments of Obstetrics/Gynecology and Pharmacology, Yale University School of Medicine, New Haven, CT, 06510, USA

    H. R. Behrman, R. F. Aten, J. J. Ireland, L. K. Soodak, J. R. Pepperell & B. Musicki

Authors
  1. H. R. Behrman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. F. Aten
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. J. Ireland
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. K. Soodak
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. R. Pepperell
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B. Musicki
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Oregon Regional Primate Research Center, Beaverton, Oregon, USA

    Richard L. Stouffer

Rights and permissions

Reprints and permissions

Copyright information

© 1987 Plenum Press, New York

About this chapter

Cite this chapter

Behrman, H.R., Aten, R.F., Ireland, J.J., Soodak, L.K., Pepperell, J.R., Musicki, B. (1987). Luteolysins and Mechanisms of Luteolysis. In: Stouffer, R.L. (eds) The Primate Ovary. Serono Symposia, USA. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-9513-7_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-9513-7_12

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4615-9515-1

  • Online ISBN: 978-1-4615-9513-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation