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. 2016 Aug 31;7:121. doi: 10.3389/fendo.2016.00121

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Copyright © 2016 Putteeraj, Soga, Ubuka and Parhar.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Interactions among the central biological clock and reproductive neurons in the hypothalamic–pituitary–gonadal axis of females. The suprachiasmatic nucleus (SCN), the central biological clock, can be divided into two major subdivisions known as the ventrolateral (vl) SCN, the core, and the dorsomedial (dm) SCN, the shell. The former contains cell bodies of vasoactive intestinal polypeptide (VIP) neurons and the latter contains cell bodies of arginine vasopressin (AVP) neurons. The vlSCN acts as the conductor of rhythmicity and transmits synchronizing cues to the dmSCN. VIP neurons project to gonadotropin-releasing hormone (GnRH) neurons in the preoptic area (POA), whereas AVP neurons project to kisspeptin (Kiss) neurons in the anteroventral periventricular nucleus (AVPV). Gonadotropin-inhibitory hormone (GnIH) neurons in the dorsomedial hypothalamus (DMH) inhibit the activity of GnRH neurons as well as kisspeptin neurons in the AVPV and arcuate nucleus (ARC). AVPV kisspeptin neuron is also regulated by stimulatory and inhibitory neurotransmitters glutamate and GABA, respectively. GnRH is released at the median eminence (ME) to stimulate luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion from the pituitary, which stimulate steroidogenesis and gametogenesis in the ovary. Estradiol (E2) secreted from the ovary gradually increases and rapidly decreases during the estrous cycle [metestrous (M), diestrus (D), proestrus (P), and estrus (E)] in rodents. GnIH and Kiss neurons express estrogen receptor (ER) to convey hormonal information to the reproductive neuronal network. ARC Kiss neurons may function as part of the negative feedback mechanism of E2 on pulsatile GnRH release at the ME. On the other hand, AVPV Kiss neurons may function as the positive feedback mechanism of high E2 concentration on GnRH/LH surge. E2 inhibits GnIH gene expression in the DMH and Kiss gene expression in the ARC but stimulates Kiss gene expression in the AVPV. Kiss and GPR54 are reported to be expressed in gonadotropes, and they are thought to exert synergic effects with GnRH and E2 on LH release (13). Solid lines indicate direct regulation by receptors of signaling molecules, whereas dotted lines indicate possible indirect regulation.