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Corticotropin-releasing factor (CRF) and stress-related reproductive failure: The brain as a state of the art or the ovary as a novel clue?

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References

  1. Selye H. Effects of adaptation to various damaging agents on the females sex organs in the rat. Endocrinology 25: 615, 1939.

    Article  CAS  Google Scholar 

  2. Rivier C., Rivier J., Vale W. Stress-induced inhibition of reproductive functions: Role of endogenous corticotropin-releasing factor. Science 231: 607, 1986.

    Article  PubMed  CAS  Google Scholar 

  3. Rivier C., Rivest S. Effect of stress on the activity of hypothalamic-pituitary-gonadal axis: periperal and central mechanisms. Biol. Reprod. 45: 523, 1991.

    Article  PubMed  CAS  Google Scholar 

  4. Genezzani A.R., Nappi R.E., Bencini S., Sgherzi M.R., Guo A.L., Criscuolo M., Trentini G.P. Immunoneuroendocrine function and reproduction. In: Genazzani A.R. et al. (Ed), Frontiers in Gynecological and Obstetric Investigation. Parthenon Publisher, Carnforth, UK, 1993, p. 357.

    Google Scholar 

  5. Chritchlow V., Liebelt A., Bar-Sela M., Mountcastle W., Lipscomb H.S. Sex differences in resting pituitary-adrenal function in the rat. Am. J. Physiol. 205: 807, 1963.

    Google Scholar 

  6. Viau V., Meaney M.J. Variations in the hypothalamus-pituitary-adrenal response to stress during the estrus cycle in the rat. Endocrinology 129: 2503, 1991.

    Article  PubMed  CAS  Google Scholar 

  7. Sawchenko P.E., Swanson L.W. Organization of CFR immunoreactive cells and fibers in the rat brain: Immunohistochemical studies. In: DeSouza E.B., C.B. Nemeroff (Ed), Corticotropin-Releasing Factor: Basic and Clinical Studies of a Neuropeptide. CRC Press, Inc., Boca Raton, Florida, 1990, p.29.

    Google Scholar 

  8. Swanson L.W. Biochemical switching in hypothalamic circuits mediating responses to stress. In: Holstege G. (Ed), Progress in Brain Research. Elsevier Science Publishers B.V. (Biochemical Division), Amsterdam, vol. 87, 1991, p.181.

    Google Scholar 

  9. Rivest S., Lee S., Rivier C., Richard D. Expression of FOS and CRF mRNA in the brain of female rats subjected to single or repeated running sessions. Soc. Neurosci Abstr. 18(1): 194, 1992.

    Google Scholar 

  10. Rivest S., Rivier C. Stress and interleukin-1β-induced activation of c-fos, NGFI-B and CRF gene expression in the hypothalamic PVN: Comparison between Sprangue-Dawley, Fisher-344 and Lewis rats. J. Neuroendocrinol. 6: 101, 1994.

    Article  PubMed  CAS  Google Scholar 

  11. Imaki T., Nahan J.L, Rivier C., Sawchenko P.E., Vale W. Differential regulation of corticotropin-releasing factor mRNA in rat brain regions by glucocorticoids and stress. J. Neurosci. 11: 583, 1991.

    Google Scholar 

  12. Imaki T., Shibasaki T., Hotta M., Demura D. Early induction of c-fos precedes increased expression of corticotropin-releasing factor messenger ribonucleic acid in the paraventricular nucleus after immobilization stress. Endocrinology 131: 240, 1992.

    PubMed  CAS  Google Scholar 

  13. Rivest S., Laflamme N. Neuronal activity and neuropeptide gene transcription in the brains of immune-challenged rats. J. Neuroendocrinol. 7: 501, 1995.

    Article  PubMed  CAS  Google Scholar 

  14. Rivest S., Torres G., Rivier C. Differential effects of central and peripheral injection of interleukin-1β on brain c-fos expression and neuroendocrine functions. Brain Research 587: 13, 1992.

    Article  PubMed  CAS  Google Scholar 

  15. Gong J., Zhang X., Jin B.Q., Huang C.S. Activation of corticotropin-releasing factor-containing neurons in the paraventricular nucleus of the hypothalamus by interleukin-1 in the rat. Neurosci. Lett. 132: 151, 1991.

    Article  Google Scholar 

  16. Ericsson A., Kovacs K.J., Sawchenko P.E. A functional anatomical analysis of central pathways subserving the effects of interleukin-1 on stress-related neuroendocrine neurons. J. Neurosci. 14: 897, 1994.

    PubMed  CAS  Google Scholar 

  17. Drolet G., Rivest S. Effect of stress on CRF and its receptor gene expression in the brain of spontaneously hypertensive rats. Soc. Neurosci. Abstr. 20: 937, 1994.

    Google Scholar 

  18. Rivest S., Rivier C. The role of CRF and interleukin-1 in the regulation of neurons controlling reproductive functions. Endocrine Rev. 16: 177, 1995.

    CAS  Google Scholar 

  19. Swanson L.W., Sawchenko P.E., Rivier J., Vale W.W. Organization of ovine corticotropin releasing factor (CRF)-immunoactive cells and fibers in the rat brain: An immunohistochemical study. Neuroendocrinology 36: 165, 1983.

    Article  PubMed  CAS  Google Scholar 

  20. Sakanaka M., Shibasaki T., Lederis K. Distribution and efferent projections of corticotropin-releasing factor-like immunoreactivity in the rat amygdaloid complex. Brain Res. 382: 213, 1986.

    Article  PubMed  CAS  Google Scholar 

  21. Simerly R.B., Swanson L.W. Projection of the medial preoptic nucleus: A phase-olus vulgaris leucoagglutinin anterograde tract-tracing study in the rat. J. Comp. Neurol. 270: 209, 1988.

    Article  PubMed  CAS  Google Scholar 

  22. Rivest S., Rivier C. Central mechanisms and sites of action involved in the inhibitory effects of CRF and cytokines on LHRH neuronal activity. In: Taché Y., Rivier C. (Ed), Corticotropin-releasing factor and cytokines: Role in the stress response. Hans Selye symposium on neuroendocrinology and stress. Annals of the New York Academic of Sciences, New York, vol. 697, 1993, p. 117.

    Google Scholar 

  23. Rivier C. Neuroendocrine effects of cytokines in the rat. Rev. in the Neurosci. 4: 223, 1993.

    Article  CAS  Google Scholar 

  24. Rivest S., Rivier C. Influence of the paraventricular nucleus of the hypothalamus in the alteration of neuroendocrine functions induced by intermittent footshock or interleukin. Endocrinology 129: 2049, 1991.

    Article  PubMed  CAS  Google Scholar 

  25. Brown M.R., Fisher L.A., Spiess J., Rivier C., Rivier J., Vale W. Corticotropin-releasing factor: actions on the symphathetic nervous system and metabolism. Endocrinology 111: 928, 1982.

    Article  PubMed  CAS  Google Scholar 

  26. Hargreaves K.M., Costello A.H., Joris J.C. Release from inflamed tissue of a substance with properties similar to corticotropin-releasing factor. Neuroendocrinology 46: 476, 1989.

    Article  Google Scholar 

  27. Karalis K., Sano H., Redwine J., Listwak S., Wilder R.L., Chrousos G.P. Autocrine or paracrine inflammatory actions of corticotropin-releasing factor in vivo. Science 254: 421, 1991.

    Article  PubMed  CAS  Google Scholar 

  28. Sasaki A., Tempst P., Liotta A.S. Isolation and characterization of a corticotropin-releasing hormone-like peptide from human placenta. J. Clin. Endocrinol. Metab. 67: 768, 1988.

    Article  PubMed  CAS  Google Scholar 

  29. Yoon D.J., Sklar C., David R. Presence of immunoreactive corticotropin-releasing factor in rat testis. Endocrinology 122: 759, 1988.

    Article  PubMed  CAS  Google Scholar 

  30. Fabbri A., Tinajero J.C., Dufau M.L. Corticotropin-releasing factor is produced by Leydig cells and has a major antireproductive role in the testis. Endocrinology 127: 1541, 1990.

    Article  PubMed  CAS  Google Scholar 

  31. Mastorakos G., Webster E.L., Friedman T.C., Chrousos G.P. Immunoreactive corticotropin-releasing hormone and its binding sites in the rat ovary. J. Clin. Invest. 92: 961, 1993.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  32. Maeda K.I., Cagampang F.R.A., Coen C.W., Tsukamura H. Involvement of the catecholaminergic input to the paraventricular nucleus and of corticotropin-releasing hormone in the fasting-induced suppression of luteinizing hormone release in female rats. Endocrinology 134: 1718, 1994.

    PubMed  CAS  Google Scholar 

  33. Walker C.D., Dallman M.F., Palmer A.A., Steele M.K. Involvement of central corticotropin-releasing factor (CRF) in suckling-induced inhibition of luteinizing hormone secretion in lactating rats. J. Neuroendocrinol. 5: 451, 1993.

    Article  PubMed  CAS  Google Scholar 

  34. Bonavera J.J., Kalra S.P., Kalra P.S. Mode of action of interleukin-1 in suppression of pituitary LH release in castrated male rats. Brain Res. 612: 1, 1993.

    Article  PubMed  CAS  Google Scholar 

  35. Rivest S., Rivier C. Interleukin-1β inhibits the endogenous expression of the early gene c-fos located within the nucleus of LHRH neurons and interferes with hypothalamic LHRH release during proestrus in the rat. Brain Res. 613: 132, 1993.

    Article  PubMed  CAS  Google Scholar 

  36. Rivier C., Vale W. Influence of corticotropin-releasing factor (CRF) on reproductive functions in the rat. Endocrinology 114: 914, 1984.

    Article  PubMed  CAS  Google Scholar 

  37. Petraglia F., Sutton S., Vale W., Plotsky P. Corticotropin-releasing factor decreases plasma LH levels in female rats by inhibiting gonadotropin-releasing hormone release into hypophysial-portal circulation. Endocrinology 120: 1083, 1987.

    Article  PubMed  CAS  Google Scholar 

  38. Rivest S., Plotsky P., Rivier C. CRF alters the infundibular LHRH secretory system from the medial preoptic area of female rats: Possible involvement of opioid receptors. Neuroendocrinology 57: 236, 1993.

    Article  PubMed  CAS  Google Scholar 

  39. Petraglia F., Locatelli V., Penalva A., Cocchi D., Genazzani A.R., Muller E.E. Gonadal steroid modulation of naloxone-induced LH secretion in the rat. J. Endocrinol. 101: 33, 1984.

    Article  PubMed  CAS  Google Scholar 

  40. Gambacciani M., Yen S.S.C., Rasmussen D.D. GnRH release from the mediobasal hypothalamus: in vitro inhibition by corticotropin-releasing factor. Neuroendocrinology 43: 533, 1986.

    Article  PubMed  CAS  Google Scholar 

  41. Feng Y.J., Shalts E., Xia L, Rivier J., Rivier C., Vale W., Ferin M. An inhibitory effect of interleukin-1α on basal gonadotropin release in the ovariectomized Rhesus monkey: Reversal by a corticotropin-releasing factor antagonist. Endocrinology 128: 2077, 1991.

    Article  PubMed  CAS  Google Scholar 

  42. Gindoff P.R., Ferin M. Endogenous opioid peptides modulate the effect of corticotropin-release factor on gonadotropin release in the primate. Endocrinology 121: 837, 1987.

    Article  PubMed  CAS  Google Scholar 

  43. Silverman A.J., Livne I., Witkin J.W. The GnRH neuronal systems: immunocytochemistry and in situ hybridization. In: Knobil E., Neill J. (Eds), The physiology of Reproduction. Raven Press, New York, vol. 1, 1994, p. 1683.

    Google Scholar 

  44. Knobil E. Editorial: Inhibition of luteinizing hormone secretion by fasting and exercise: “Stress” or specific metabolic signals? Endocrinology 132: 1879, 1993.

    Article  PubMed  CAS  Google Scholar 

  45. Rivest S., Richard D. Involvement of corticotropin-releasing factor in the anorexia induced by exercise. Brain Res. Bull. 25: 169, 1990.

    Article  PubMed  CAS  Google Scholar 

  46. Rivest S., Richard D. Hypothalamic paraventricular nucleus lesions di not prevent anorectic effect of exercise in male rats. Am. J. Physiol. 259 (regulatory Integrative Comp. Physiol. 28): R579, 1990.

    PubMed  CAS  Google Scholar 

  47. Rivest S., Deshaies Y., Richard D. The effects of corticotropin-releasing factor on energy balance in rats are sex-dependent. Am. J. Physiol. 257 (Regulatory Integrative Comp. Physiol. 26): R1417, 1989.

    PubMed  CAS  Google Scholar 

  48. Rivest S., Landry J., Richard D. Effect of exercise training on energy balance of orchidectomized rats. Am. J. Physiol. 257 (Regulatory Integrative Comp. Physiol. 26): R550, 1989.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  50. Chen M.D., O’Byrne K.T., Chiappini S.E., Hotchkiss J., Knobil E. Hypoglycemic “stress” and gonadotropin-releasing hormone pulse generator activity in the rhesus monkey: role of the ovary. Neuroendocrinology 56: 666, 1992.

    Article  PubMed  CAS  Google Scholar 

  51. Norman R.L., Smith C.J. Restraint inhibits luteinizing hormone and testosterone secretion in intact male macaques: effects of concurrent naloxone administration. Neuroendocrinology 55: 405, 1992.

    Article  PubMed  CAS  Google Scholar 

  52. Patchev V.K., Hayashi S., Orisaka C., Almeioda O.F.X. Implications of estrogen-dependent brain organization for gender differences in hypothalamo-pituitary-adrenal regulation. FASEB J. 9: 419, 1995.

    PubMed  CAS  Google Scholar 

  53. MacLusky N.J., Naftolin F. Sexual differentation of the central nervous system. Science 211: 1294, 1981.

    Article  PubMed  CAS  Google Scholar 

  54. Hiroshige T., Wada-Okada S. Diurnal changes of hypothalamic content of corticotrophin-releasing activity in female rats at various stages of the estrous cycle. Neuroendocrinology 12: 316, 1973.

    Article  PubMed  CAS  Google Scholar 

  55. Hiroshige T., Abe K., Wada S., Kanedo M. Sex difference in circadian periodicity of CRF activity in the rat hypothalamus. Neuroendocrinology 11: 306, 1973.

    Article  PubMed  CAS  Google Scholar 

  56. Haas D.A., George S.R. Gonadal regulation of corticotropin-releasing factor immunoreactivity in hypothalamus. Brain Res. Bull. 20: 361, 1988.

    Article  PubMed  CAS  Google Scholar 

  57. Watts A.G., Swanson L.W. Diurnal variations in the content of preprocorticotropin-releasing hormone messenger ribonucleic acids in the hypothalamic paraventricular nucleus of rats of both sexes as measured by in situ hibridization. Endocrinology 125: 1734, 1989.

    Article  PubMed  CAS  Google Scholar 

  58. Buckingham J.C., Dohler K.-D., Wilson C.A. Activity of the pituitary-adrenocortical system and thyroid gland the oestrus cycle of the rat. J. Endocrinol. 78: 359, 1978.

    Article  PubMed  CAS  Google Scholar 

  59. Coney M.D., Kitay J.I. Effect of ovariectomy on pituitary secretion of ACTH. Endocrinology 85: 1097, 1969.

    Article  Google Scholar 

  60. Kitai J.I Effect of estradiol pituitary-adrenal function in male and female rats. Endocrinology 72: 947, 1963.

    Google Scholar 

  61. Bohler H.C.L.J., Zoeller R.T., King J.C., Rubin B.S., Weber R., Merrian G.R. Corticotropin-releasing hormone mRNA is elevated on the afternoon of proestrus in the parvocellular paraventricular nuclei of the female rat. Mol. Brain. Res. 8: 259, 1990.

    Article  PubMed  CAS  Google Scholar 

  62. Almeida O.F.X., Hassan A.H.S., Harbuz M.S., Linton E.A., Lightman S.L. Hypothalamic corticotropin-releasing hormone and opioid peptide neurons: functional changes after adrenalectomy and/or castration. Brain Res. 571: 189, 1992.

    Article  PubMed  CAS  Google Scholar 

  63. Genazzani A.R., Lemarchand-Bereaud T.H., Aubert M.L., Feibert J.P. Pattern of plasma ACTH, GH, and cortisol during the mestrual cycle. J. Clin. Endocrinol. Metab. 41: 1975.

  64. Marinari K.T., Leshner A.I., Doyle M.P. Menstrual cycle status and adrenocortical reactivity to stress. Psychoneuroendocrinology 1: 213, 1976.

    Article  PubMed  CAS  Google Scholar 

  65. Biller B.M.K., Federoff H.J., Koening J.I., Klibanski A. Abnormal cortisol secretion and responses to corticotropin-releasing hormone in women with hypothalamic amenorrhea. J. Clin. Endocrinol. Metab. 70: 311, 1990.

    Article  PubMed  CAS  Google Scholar 

  66. Nappi R.E., Petraglia F., Genazzani A.D., D’Ambrogio G., Zara C., Genazzani A.R. Hypothalamic amenorrhea: evidence of a central derangement of hypothalamic-pituitary-adrenal cortex axis activity. Fertil. Steril. 59: 571, 1993.

    PubMed  CAS  Google Scholar 

  67. Plotsky P., Cunningham E.T.J., Widmaier E.P. Catecholamnergic modulation of corticotropin-releasing factor and adrenocorticotropin secretion. Endocr. Rev. 10: 437, 1989.

    Article  PubMed  CAS  Google Scholar 

  68. Vamvakopoulos N.C., Chrousos G.P. Evidence of direct estrogenic regulation of human corticotropin releasing hormone gene expression: potential implications for the sexual dimorphism of the response and immune/inflammatory reaction. J. Clin. Invest. 92: 1986, 1993.

    Article  Google Scholar 

  69. Rivest S., Laflamme N., Nappi R.E. Immune challenge and immobilization stress induce transcription of the gene encoding the CRF receptor in selective nuclei of the rat hypothalamus. J. Neurosci. 15: 2680, 1995.

    PubMed  CAS  Google Scholar 

  70. Nappi R.E., Rivest S. Ovulatory cycles influences the stimulatory effect of stress on the expression of corticotropin-releasing receptor messenger ribonucleic acid in the paraventricular nucleus of the female rat hypothalamus. Endocrinology 136: 4073, 1995.

    PubMed  CAS  Google Scholar 

  71. Vamvakopoulos N.C., Chrousos G.P. Hormonal regulation of human corticotropin-releasing hormone gene expression: implications for the stress response and immune/inflammatory reaction. Endocr. Rev. 15: 409, 1994.

    Article  PubMed  CAS  Google Scholar 

  72. Cintra A., Fuxe K., Harfstrand A., Agnati L.F., Miller L.S., Greene J.L., Gustafsson J.A. On the cellular localization and distribution of estrogen receptors in the rat tel- and diecephalon using monoclonal antibodies to human estrogen receptor. Neurochem. Int. 8: 587, 1986.

    Article  PubMed  CAS  Google Scholar 

  73. Simerly R.B., Chang C., Muramatsu M., Swanson L.W. Distribution of androgen and estrogen receptor mRNA-containing cells in the rat brain: an in situ hybridization study. J. Comp. Neurol. 294: 76, 1990.

    Article  PubMed  CAS  Google Scholar 

  74. Sar M., Parikh I. Immunohistochemical localization of estrogen receptor in rat brain, pituitary and uterus with monoclonal antibodies. J. Steroid Biochem. 24: 497, 1986.

    Article  PubMed  CAS  Google Scholar 

  75. Corodimas K.P., Morrell J.I. Estradiol-concentrating forebrain and midbrain neurons project directly to the medulla. J. Comp. Neurol. 291: 602, 1990.

    Article  Google Scholar 

  76. Palkovits M. Anatomy of neural pathways affecting CRH secretion. Ann. NY Acad Sci. 512:139, 1987.

    Article  PubMed  CAS  Google Scholar 

  77. Rainbow T.C., Parsons B., MacLusky N.J., McEwen B.S. Estradiol receptor levels in rat hypothalamic and limbic nuclei. J. Neurosci. 2: 1439, 1982.

    PubMed  CAS  Google Scholar 

  78. Herbison A.E., Theodosis D.T. Absence of estrogen receptor immunoreactivity in somastatin (SRIF) neurons of the periventricular nucleus but sexually dimorphic colocalization of estrogen and SRIF immunoreactivities in neurons of the bed nucleus of the stria terminalis. Endocrinology 132: 1707, 1993.

    PubMed  CAS  Google Scholar 

  79. Rivier C., Vale W. Effect of the long-term administration of corticotropin-releasing factor on the pituitary-adrenal and pituitary-gonadal axis in the male rat. J. Clin. Invest. 75: 689, 1985.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  80. Thompson R., Seasholtz A., Douglas J., Herbert E. Cloning and distribution of expression of the rat corticotropin-releasing factor (CRF) gene. In: DeSouza E., Nemeroff C. (Eds), Corticotropin-releasing factor: basic and clinical studies of a neuropeptide. CRC, Boca Raton, 1990, p. 1.

    Google Scholar 

  81. Ulisse S., Fabbri A., Dufau M.L. Corticotropin-releasing factor receptors and action in rat Leydig cells. J. Biol.Chem. 264: 2156, 1989.

    PubMed  CAS  Google Scholar 

  82. Dufau M.L., Tinajero J.C., Fabbri A. Corticotropin-releasing factor: an antireproductive hormone of the testis. FASEB J. 7: 299, 1993.

    PubMed  CAS  Google Scholar 

  83. Mastorakos G., Scopa C.D., Vryonidu A., Friedman T.C., Kattis D., Phenekos C., Merino M.J., Chrousos G.P. Presence of immunoreactive corticotropin-releasing hormone in normal and polycystic human ovaries. J. Clin. Endocrinol. Metab. 79: 1191, 1994.

    PubMed  CAS  Google Scholar 

  84. Nappi R.E., Rivest S. Stress-induced genetic expression of corticotropin-releasing factor-receptor within the rat ovaries: an effect dependent on the ovulatory cycle. Biol. Reprod. 53: 1417, 1995.

    Article  PubMed  CAS  Google Scholar 

  85. Calogero A.E., Burrello N., Papale L., Palumbo M., Cianci A., Sanfilippo S., D’Agata R. Corticotropin-releasing hormone inhibits estrogen production from rat granulosa and human granulosaluteal cells in vitro. J. Endocrinol Invest. 16: 5, 1993.

    Google Scholar 

  86. Mastorakos G., Kokia E., Patchev V., Webster E.L., Redwine J., Adashi E.Y., Chrousos G.P. Presence of immunoreactive CRH and CRH binding sites, and evidence for auto/paracrine action of this neuropeptide in the rat ovary. San Antonio, Texas, 1992, p. 246.

  87. Burder H.W. The adrenergic innervation of mammalian ovaries. In: Ben-Jonathan N., Bahar J.M., Weiner R.I. (Eds), Catecholamines as hormone Regulators. Raven Press, New York, 1985, p. 279.

    Google Scholar 

  88. Merchenthaler I., Hynes M.A. Vigh S., Schally A.V., Petrusz P. Immunocytochemical localization of corticotropin-releasing factor (CRF) in the rat spinal cord. Brain Res. 275: 373, 1983.

    Article  PubMed  CAS  Google Scholar 

  89. Ojeda S.R., Lara H.E. The role of the sympathetic nervous system in the regulation of ovarian function. In: Pirke K.M., Wuttke W., Schweiger U. (Eds) The mestrual cycle and its disorders. Springer-Verlag, Berlin, 1989, p. 26.

    Chapter  Google Scholar 

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Nappi, R.E., Rivest, S. Corticotropin-releasing factor (CRF) and stress-related reproductive failure: The brain as a state of the art or the ovary as a novel clue?. J Endocrinol Invest 18, 872–880 (1995). https://doi.org/10.1007/BF03349836

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