Sexually differentiated neural systems controlling the preovulatory release of gonadotropin

Current Opinion in Endocrinology and Diabetes

Volumn 3, Issue 2, 1996, Pages 171-177

  Simerly, Richard B ^a,b  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^b OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0011308732     PISSN: 10683097     EISSN: None     Source Type: Journal    
DOI: 10.1097/00060793-199604000-00016     Document Type: Article

References (74)

1. Harris GW: Neural control of the pituitary gland. Physiol Rev 1948, 28:139-179.
2. Sawyer CH: History of the neurovascular concept of hypothalamohypophysial control. Biol Reprod 1978, 18:325-328.
3. Swanson LW: Organization of mammalian neuroendocrine system. In Handbook of Physiology: The Nervous System IV. Edited by Björklund A, Hökfelt T, Swanson LW. Baltimore: Waverty Press; 1986:317-363.
4. Simerly RB: Anatomical substrates of hypothalamic integration. In The Rat Nervous System. Edited by Paxinos G. San Francisco: Academic Press; 1995:353-376.
5. Harris GW, Levine S: Sexual differentiation of the brain and its experimental control. J Physiol 1965, 181:379-400.
6. Swaab DF, Hofman MA: Sexual differentiation of the human hypothalamus in relation to gender and sexual orientation. Trends Neurosci 1995, 18:264-270. This paper provides a critical evaluation of recent observations on sexually dimorphic structures in the human hypothalamus. The demonstration that marked sex differences in brain morphology exist in humans has brought a great deal of interest to the overall field of sexual differentiation. This paper does a particularly good job of reviewing recent results in this controversial field and discusses inherent problems in studying postmortem brain samples. In addition, the results are discussed within the overall context of the development of functional sex differences in reproduction, gender, and sexual orientation.
7. Breedlove SM: Sexual dimorphism in the vertebrate nervous system. J Neurosci 1992, 12:4133-4142.
8. Tobet SA, Fox TO: Sex differences in neuronal morphology influenced hormonally throughout life. In Handbook of Behavioral Neurobiology, vol 11: Sexual Differentiation. Edited by Gerall AA, Moltz H, Ward IL. New York: Plenum Press; 1992:41-83.
9. Panzica GC, Viglietti-Panzica C, Calcagni M, Anselmetti GC, Schumacher M, Balthazart J: Sexual differentiation and hormonal control of the sexually dimorphic medial preoptic nucleus in the quail. Brain Res 1987, 416:59-68.
10. DeVoogd TJ: Endocrine modulation of the development and adult function of the avian song system. Psychoneuroendocrinology 1991, 16:41-66.
11. Arnold AP, Gorski RA: Gonadal steroid induction of structural sex differences in the central nervous system. Annu Rev Neurosci 1984, 7:413-442.
12. Crews D, Robker R, Mendonça M: Seasonal fluctuations in brain nuclei in the red-sided garter snake and their hormonal control. J Neurosci 1993, 13:5256-5364.
13. Kelley DB: The genesis of male and female brains. Trends Neurosci 1986, 9:499-502.
14. Frankfurt M: Gonadal steroids and neuronal plasticity. Ann N Y Acad Sci 1995, 743:45-60. This paper reviews recent observations on the role of gonadal steroids in regulating neuronal morphologic plasticity in the adult rat hypothalamus. Results show that neurons in the hypothalamus are capable of rapid and reversible structural alterations such as those that are typically ascribed to earlier periods in development. Significantly, intact cycling female animals are utilized to demonstrate changes in spine density on individual hypothalamic neurons, which may contribute to altered responsiveness of these cells during the estrus cycle.
15. Juraska JM: Sex differences in "cognitive" regions of the rat brain. Psychoneuroendocrinology 1991, 16:105-119.
16. Barraclough CA: Sex differentiation of cyclic gonadotropin secretion. In Advances in the Biosciences, vol 25. Edited by Kaye AM, Kaye M. Oxford: Pergamon Press; 1979:433-450.
17. Fink G: The G.W. Harris Lecture: steroid control of brain and pituitary function. Q J Exp Physiol 1988, 73:257-293.
18. Simerly RB: Hormonal regulation of limbic and hypothalamic pathways. In Neurobiological Effects of Sex Steroid Hormones. Edited by Micevych PE, Hammer RP Jr. Cambridge, England: Cambridge University Press; 1995:85-114. This chapter reviews information on the neuroanatomic organization of sexually dimorphic pathways in the forebrain of the rat. In addition, hormonal regulation and possible sex differences in the expression of steroid hormone receptors within this circuitry are also discussed. This review also includes a detailed description of experimental evidence that argues for a critical role for the AVPV in the regulation of the preovulatory secretion of luteinizing hormone.
19. Gerall AA, Givon L: Early androgen and age-related modifications in female rat reproduction. In Handbook of Behavioral Neurobiology. Edited by Gerall AA, Moltz H, Ward IL. New York: Plenum Press; 1992:313-354.
20. Shivers BD, Harlan RE, Morrell JI, Pfaff DW: Absence of oestradiol concentration in cell nuclei of LHRH immunoreactive neurones. Nature 1983, 304:345-347.
21. Wray S, Hoffman G: A developmental study of the quantitative distribution of LHRH neurons within the central nervous system of the postnatal male and female rats. J Comp Neurol 1986, 252:522-531.
22. Wray S, Gainer H: Effect of neonatal gonadectomy on the postnatal development of LHRH cell subtypes in male and female rats. Neuroendocrinology 1987, 45:413-419.
23. Kalra SP: Mandatory neuropeptide-steroid signaling for the preovulatory luteinlzing hormone-releasing hormone discharge. Endocr Rev 1993, 14:507-538.
24. Swaab DF: Development of the human hypothalamus. Neurochem Res 1995, 20:509-519.
25. Madeira MD, Sousa N, Santer RM, Paula-Barbosa MM, Gundersen HJG: Age and sex do not affect the volume, cell numbers, or cell size of the suprachiasmatic nucleus of the rat: an unbiased stereological study. J Comp Neurol 1995, 361:585-601.
26. Watts AG, Swanson LW, Sanchez-Watts G: Efferent projections of the suprachiasmatic nucleus: I: studies using anterograde transport of Phaseolus vulgaris leucoagglutinin in the rat. J Comp Neurol 1987, 258:204-229.
27. Watson RE Jr, Wiegand SJ, Clough RW, Sladek CD, Hoffman-Small G: The sexually dimorphic vasopressinergic fiber density in the medial preoptic nucleus originates in the suprachiasmatic nucleus [abstract]. Soc Neurosci Abstr 1984, 10:436.
28. Power RF, Mani SK, Codina J, Conneely OM, O'Malley BW: Dopaminergic and ligand-independent activation of steroid hormone receptors. Science 1991, 254:1636-1639.
29. Fink G: Gonadotropin secretion and its control. In The Physiology of Reproduction. Edited by Knobil E, Neill J. New York: Raven Press; 1988:1349-1376.
30. Kalra SP, Kalra PS: Neural regulation of luteinizing hormone secretions in the rat. Endocr Rev 1983, 4:311-351.
31. Everitt BJ, Meister B, Hökfelt T, Melander T, Terenius L, Rökaeus A, Theodorsson Norheim E, Dockray G, Edwardson J, Cuello C: The hypothalamic arcuate nucleus-median eminence complex: immunohistochemistry of transmitters, peptides and DARPP-32 with special reference to coexistence in dopamine neurons. Brain Res 1986, 396:97-155.
32. Simerly RB: Distribution and regulation of steroid hormone receptor gene expression in the central nervous system. In Advances in Neurology, vol 59. Edited by Seil FJ. New York: Raven Press; 1993:207-226.
33. Matsumoto A: Synaptogenic action of sex steroids in developing and adult neuroendocrine brain. Psychoneuroendocrinology 1991, 16:25-40.
34. Gorski RA: Localization and sexual differentiation of the nervous structures which regulate ovulation. J Reprod Fertil 1966, 1:67-88.
35. Gu G, Simerly RB: Hormonal regulation of opioid peptide neurons in the anteroventral periventricular nucleus. Horm Behav 1994, 28:503-511.
36. Bleier R, Byne W, Siggelkow I: Cytoarchitectonic sexual dimorphisms of the medial preoptic and anterior hypothalamic areas in guinea pig, rat, hamster, and mouse. J Comp Neurol 1982, 212:118-130.
37. Terasawa E, Davis GA: The LHRH neuronal system in female rats: relation to the medial preoptic nucleus. Endocrinol Jpn 1983, 30:405-417.
38. Simerly RB, Swanson LW: The distribution of neurotransmitter-specific cells and fibers in the anteroventral periventricular nucleus: implications for the control of gonadotropin secretion in the rat. Brain Res 1987, 400:11-34.
39. Wiegand SJ, Terasawa E: Discrete lesions reveal functional heterogeneity of suprachiasmatic structures in regulation of gonadotropin secretion in the female rat. Neuroendocrinology 1982, 34:395-404.
40. Popolow HB, King JC, Gerall AA: Rostral medial preoptic area lesions' influence on female estrous processes and LHRH distribution. Physiol Behav 1981, 27:855-861.
41. Ronnekleiv OK, Kelly MJ: Luteinizing hormone releasing hormone neuronal system during the estrous cycle of the female rat: effects of surgically induced persistent estrus. Neuroendocrinology 1986, 43:564-576.
42. Blaustein JD, Olster DH: Gonadal steroid hormone receptors and social behaviors. In Advances in Comparative and Environmental Physiology, vol 3. Edited by Balthazart J. Berlin: Springer-Verlag; 1989:31-104.
43. Akema T, Tadakoro Y, Kimura F: Regional specificity in the effect of estrogen implantation within the forebrain on the frequency of pulsatile luteinizing hormone secretion in the ovariectomized rat Neuroendocrinology 1984, 39:517-523.
44. Peterson SL, Barraclough CA: Suppression of spontaneous luteinizing hormone surges in estrogen-trested ovariectomized rats by microimplants of antiestrogens into the preoptic brain. Brain Res 1989, 484:279-289.
45. Kubo K, Gorski RA, Kawakami M: Effects of estrogen on neuronal excitability in the hippocampal-septalhypothalamic system. Neuroendocrinology 1975, 18:176-191.
46. Everett JW: The timing of ovulation. J Endocrinol 1977, 75:1P-13P.
47. Simerly RB, Young BJ, Capozza MA, Swanson LW: Estrogen differentially regulates neuropeptide gene expression in a sexually dimorphic olfactory pathway. Proc Natl Acad Sci U S A 1989, 86:4766-4770.
48. Simerly RB: Hormonal control of neuropeptide gene expression in sexually dimorphic olfactory pathways. Trends Neurosci 1990, 13:104-110.
49. Gu GB, Simerly RB: Efferent connections of the anteroventral periventricular nucleus of the hypothalamus in the female rat [abstract]. Soc Neurosci Abstr 1994, 20:1739.
50. Lee W-S, Smith MS, Hoffman GE: Luteinizing hormone-releasing hormone neurons express Fos protein during the proestrous surge of luteinizing hormone. Proc Natl Acad Sci U S A 1990, 87:5163-5167.
51. King JC, Rubin BS: Dynamic alterations in luteinizing hormone-releasing hormone (LHRH) neuronal cell bodies and terminals of adult rats. Cell Mol Biol 1995, 15:89-106. This paper reviews morphologic data documenting that marked changes in morphology and cellular relationships of GnRH-containing neurons occur in response to hormone treatment and during the estrus cycle. Moreover, evidence is presented that argues for a central subpopulation of GnRH-containing neurons that appear to be particularly important in initiating the proestrus surge in luteinizing hormone secretion. In addition, recent findings obtained using confocal microscopy reveal that GnRH-containing terminals are prevented from contacting the basal lamina of the brain by glial endfeet and that these structural relationships change as a function of endocrine status.
52. Wang H-J, Hoffman GE, Smith MS: Increased GnRH mRNA in the GnRH neurons expressing cFos during the proestrous luteinizing hormone surge. Endocrinology 1995, 136:3673-3676. This paper reports histochemical findings that demonstrate a significant induction in GnRH mRNA within a subpopulation of GnRH neurons defined by coexpression of c-fos immunoreactivity. Thus, although steroid hormones do not significantly alter expression of GnRH mRNA in the population as a whole, changes in the hormone environment correlate with altered GnRH expression in a subpopulation of preoptic neurons that appear to be transsynaptically activated.
53. Kordon C, Drouva SV, de la Escalera GM, Weiner RI: Role of classic and peptide neuromediators in the neuroendocrine regulation of luteinizing hormone and prolactin. In The Physiology of Reproduction, edn 2. Edited by Knobil E, Neill JD. New York: Raven Press; 1994:1621-1681.
54. Simerly RB, McCall LD, Watson SJ: The distribution of opioid peptides in the preoptic region: Immunohistochemical evidence for a steroid sensitive enkephalin sexual dimorphism. J Comp Neurol 1988, 276:442-459.
55. Simerly RB, Swanson LW: Projections of the medial preoptic nucleus: a Phaseolus vulgaris leucoagglutinin anterograde tract-tracing study in the rat. J Comp Neurol 1988, 270:209-242.
56. Lisciotto CA, Morrell JI: Sex differences in the distribution and projections of testosterone target neurons in the medial preoptic area and the bed nucleus of the stria terminalis of rats. Horm Behav 1994, 28:492-502. This paper describes the results of combined retrograde tract tracing-steroid hormone autoradiographic studies on sex differences in hormone-sensitive projections to the midbrain from the medial preoptic nucleus and bed nuclei of the stria terminalis. The results demonstrate that these two structures, which contain more neurons in male rats relative to homologous structures in female rats, also have proportionally more testosterone target neurons that project to the midbrain in male animals.
57. Reinoso BS, Simerly RB: Hormone-sensitive sexually dimorphic neurons in the anteroventral periventricular nucleus project to the arcuate nucleus of the hypothalamus. Soc Neurosci Abstr 1991, 17:1229.
58. Canteras NS, Simerly RB, Swanson LW: Organization of projections from the medial nucleus of the amygdala: a phal study in the rat. J Comp Neurol 1995, 360:213-245. This paper describes the results of anterograde tract tracing studies on the projections of each part of the medial nucleus of the amygdala. The results describe especially strong projections to other sexually dimorphic regions in the forebrain that contain high densities of neurons that express estrogen and androgen receptors, including prominent projections to the AVPV and the ventral premamillary nucleus of the hypothalamus.
59. Hines M, Allen LS, Gorski RA: Sex differences in subregions of the medial nucleus of the amygdala and the bed nucleus of the stria terminalis of the rat. Brain Res 1992, 579:321-326.
60. Ganteras NS, Simerly RB, Swanson LW: Projections of the ventral premamillary nucleus. J Comp Neurol 1992, 324:195-212.
61. Beltramino C, Taleisnik S: Release of LH in the female rat by olfactory stimuli. Neuroendocrinology 1983, 36:53-58.
62. Akesson TR, Micevych PE: Sex steroid regulation of tachyklnin peptides in neuronal circuitry mediating reproductive functions. In Neurobiological Effects of Sex Steroid Hormones. Edited by Micevych PE, Hammer RP Jr. Cambridge: University Press; 1995:207-233. This chapter reviews a variety of observations on steroidal regulation of tachykinin expression in sexually dimorphic pathways of the rodent forebrain. In addition, recent findings on sex differences in tachykinin expression in the ventral premamillary nucleus are also described. Specifically, female rodents were found to have approximately half the number of tachykinin-immunoreactive cells in the ventral premamillary nucleus relative to male rodents. The results of a behavioral analysis are also described in which excitotoxin lesions were used to demonstrate the importance of the ventral premamillary nucleus in male copulatory behavior. The possible involvement of this nucleus in regulating luteinizing hormone secretion was not evaluated.
63. Toran-Allerand CD: On the genesis of sexual differentiation of the central nervous system: morphogenetic consequences of steroidal exposure and possible role of α-fetoprotein. Prog Brain Res 1984, 61:63-98.
64. Toran-Allerand CD, Ellis L, Pfenninger KH: Estrogen and insulin synergism in neurite growth enhancement in vitro: mediation of steroid effects by interactions with growth factors? Dev Brain Res 1986, 41:87-100.
65. Ojeda SR, Ma YJ: The role of growth factors in the neuroendocrine control of female sexual development. Curr Opin Endocrinol Diabetes 1995, 2:148-156. This paper discusses recent evidence implicating astrocytes and growth factors secreted by these cells in regulating development of GnRH neuronal function. A model is proposed for neurotransmitter activation not only of GnRH-containing neurons, but also of astrocytes that release growth factors that activate GnRH neurons through other neuroactive substances such as prostaglandins. The authors propose that this cascade of cellular events is an essential component of the GnRH neuronal activation that occurs during the onset of puberty.
66. Garcia-Segura LM, Duenas M: Gonadal hormone regulation of neuronal-glial interactions in the developing neuroendocrine hypothalamus. J Steroid Biochem Mol Biol 1995, 53:293-298. This paper describes a series of studies that document the influence of gonadal steroids on astroglial cells in the hypothalamus. Significantly, in the arcuate nucleus of the rat, perinatal androgen exposure alters gene expression and morphologic differentiation of astroglia, which may contribute to the development of sex-specific alterations in synaptic contacts in this important neuroendocrine nucleus.
67. Torres-Aleman I, Rejas MT, Pons S, Garcia-Segura LM: Estradiol promotes cell shape changes and glial fibrillary acidic protein redistribution in hypothalamic astrocytes in vitro: a neuronal-mediated effect. Glia 1992, 6:180-187.
68. Colamarino SA, Tessier-Lavigne M: The role of the floor plate in axon guidance. Annu Rev Neurosci 1995, 18:497-529.
69. Steindler DA: Glial boundaries in the developing nervous system. Annu Rev Neurosci 1993, 16:445-470.
70. Toran-Allerand CD: Developmental interactions of estrogens with neurotrophins and their receptors. In Neurobiological Effects of Sex Steroid Hormones. Edited by Micevych PE, Hammer RPJr. Cambridge: University Press; 1995:391-411. This paper reviews anatomic, cellular, and molecular relationships between estrogen and neurotrophins or their receptors. The author was one of the first to suggest that estrogen may influence brain development and function through interactions with neurotrophins. The results of experiments utilizing in vivo, tissue culture, and transformed cell lines as model systems are discussed within the overall context of estrogen's role in regulating brain plasticity. The broad perspective illustrated in this review makes the point that sexual differentiation is just one of the ways that sex steroid hormones alter brain structure and function.
71. Lustig RH: Sex hormone modulation of neural development in vitro. Horm Behav 1994, 28:383-395.
72. Kusano K, Fueshko S, Gainer H, Wray S: Electrical and synaptic properties of embryonic luteinizing hormone-releasing hormone neurons in expiant cultures. Proc Natl Acad Sci U S A 1995, 92:3918-3922. This paper describes an electrophysiologic evaluation of GnRH neurons in explant cultures derived from olfactory pit regions of embryonic mice. Through the application of various pharmacologie, tools the authors demonstrate that even embryonic GnRH neurons that have not yet achieved their mature postnatal environment display a highly differentiated repertoire of responses mediated by voltage- and ligand-gated channels. In addition, the authors report that pulsatile activity is an intrinsic property of these cells, and that dye coupling between embryonic GnRH neurons was not observed in any of these experiments. These results are discussed within the context of the development of networks of GnRH neurons and possible approaches to defining the biophysical properties of GnRH neurons within these networks.
73. Bolz J, Götz M, Hübener M, Novak N: Reconstructing cortical connections in a dish. Trends Neurosci 1993, 16:310-315.
74. Wray S: Use of organotypic cultures for the study of neuroendocrine cells. Methods Neurosci 1994, 20:13-44.