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Review
. 2016 Jul;28(7):10.1111/jne.12405.
doi: 10.1111/jne.12405.

Peripheral and Central Mechanisms Involved in the Hormonal Control of Male and Female Reproduction

L M Rudolph  1 , G E Bentley  2 , R S Calandra  3 , A H Paredes  4 , M Tesone  3 , T J Wu  5 , P E Micevych  1
Affiliations
Review

Peripheral and Central Mechanisms Involved in the Hormonal Control of Male and Female Reproduction

L M Rudolph et al. J Neuroendocrinol. 2016 Jul.

Abstract

Reproduction involves the integration of hormonal signals acting across multiple systems to generate a synchronised physiological output. A critical component of reproduction is the luteinising hormone (LH) surge, which is mediated by oestradiol (E2 ) and neuroprogesterone interacting to stimulate kisspeptin release in the rostral periventricular nucleus of the third ventricle in rats. Recent evidence indicates the involvement of both classical and membrane E2 and progesterone signalling in this pathway. A metabolite of gonadotrophin-releasing hormone (GnRH), GnRH-(1-5), has been shown to stimulate GnRH expression and secretion, and has a role in the regulation of lordosis. Additionally, gonadotrophin release-inhibitory hormone (GnIH) projects to and influences the activity of GnRH neurones in birds. Stress-induced changes in GnIH have been shown to alter breeding behaviour in birds, demonstrating another mechanism for the molecular control of reproduction. Peripherally, paracrine and autocrine actions within the gonad have been suggested as therapeutic targets for infertility in both males and females. Dysfunction of testicular prostaglandin synthesis is a possible cause of idiopathic male infertility. Indeed, local production of melatonin and corticotrophin-releasing hormone could influence spermatogenesis via immune pathways in the gonad. In females, vascular endothelial growth factor A has been implicated in an angiogenic process that mediates development of the corpus luteum and thus fertility via the Notch signalling pathway. Age-induced decreases in fertility involve ovarian kisspeptin and its regulation of ovarian sympathetic innervation. Finally, morphological changes in the arcuate nucleus of the hypothalamus influence female sexual receptivity in rats. The processes mediating these morphological changes have been shown to involve the rapid effects of E2 controlling synaptogenesis in this hypothalamic nucleus. In summary, this review highlights new research in these areas, focusing on recent findings concerning the molecular mechanisms involved in the central and peripheral hormonal control of reproduction.

Keywords: androgens; autocrine; oestrogens; paracrine; progesterone.

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Figures

Fig. 1
Fig. 1
A model showing proposed actions of oestradiol (E2) on hypothalamic cells. In kisspeptin (Kiss1) neurones, E2 acts at both membrane and nuclear oestrogen receptors. During di-oestrus, classical nuclear E2 signalling induces progesterone receptor (PR) expression in Kiss1 neurones in the rostral periventricular nucleus of the third ventricle (RP3V). On pro-oestrus, rising E2 leads to transactivation of mGluR1a in astrocytes, which increases [Ca2+]i, leading to the conversion of cholesterol to pregnenolone (PREG) by the P450scc enzyme and the conversion of PREG to progesterone (neuroP) by 3β-hydroxysteroid dehydrogenase (HSD). Simultaneously, E2 activates an oestrogen receptor (ER)α-mGluR1a complex in neurones leading to the expression of Kiss1. Newly synthesised neuroP diffuses out of the astrocytes and activates E2-induced PR, which has been trafficked to the Kiss1 neuronal membrane. This leads to a series of events culminating in Kiss1 secretion onto GPR54 expressing gonadotrophin-releasing hormone (GnRH) neurones. Signalling through PR in Kiss1 neurones induces Kiss1 release, activating GnRH neurones and triggering the E2-induced luteinising hormone (LH) surge from anterior pituitary gonadotrophs. MAPK, mitogen-activated protein kinase.
Fig. 2
Fig. 2
Gonadotropin-Releasing Hormone (GnRH) peptide processing and action. The decapeptide, GnRH, is processed extracellularly to form the metabolite, GnRH-(1-5) by the zinc metalloendopeptidase, EC3.4.24.15 (EP24.15; 66, 73). The metabolite, GnRH-(1-5), exerts is biological activities via 2 putative receptors, the G-protein coupled receptors (GPR) GPR101 and GPR173 (70, 71).
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References

    1. Kuo J, Micevych P. Neurosteroids, trigger of the LH surge. J Steroid Biochem Mol Biol. 2012;131:57–65. - PMC - PubMed
    1. Brom GM, Schwartz NB. Acute changes in the estrous cycle following ovariectomy in the golden hamster. Neuroendocrinology. 1968;3:366–377. - PubMed
    1. Ferin M, Tempone A, Zimmering PE, Van de Wiele RL. Effect of antibodies to 17beta-estradiol and progesterone on the estrous cycle of the rat. Endocrinology. 1969;85:1070–1078. - PubMed
    1. Labhsetwar AP. Role of estrogens in ovulation: a study using the estrogen-antagonist, I.C.I. 46,474. Endocrinology. 1970;87:542–551. - PubMed
    1. Micevych P, Sinchak K, Mills RH, Tao L, LaPolt P, Lu JK. The luteinizing hormone surge is preceded by an estrogen-induced increase of hypothalamic progesterone in ovariectomized and adrenalectomized rats. Neuroendocrinology. 2003;78:29–35. - PubMed