TY - JOUR
T1 - Estrogenic regulation of reproduction and energy homeostasis by a triumvirate of hypothalamic arcuate neurons
AU - Stincic, Todd L.
AU - Kelly, Martin J.
N1 - Funding Information:
We thank current and former colleagues who contributed to the work described herein. Research reported in this publication was supported by National Institute of Health R01 grants NS 38809 (MJK), NS 43330 (Oline K Rønnekleiv) and DK 68098 (MJK and Oline K Rønnekleiv).
Publisher Copyright:
© 2022 British Society for Neuroendocrinology.
PY - 2022/6
Y1 - 2022/6
N2 - Pregnancy is energetically demanding and therefore, by necessity, reproduction and energy balance are inextricably linked. With insufficient or excessive energy stores a female is liable to suffer complications during pregnancy or produce unhealthy offspring. Gonadotropin-releasing hormone neurons are responsible for initiating both the pulsatile and subsequent surge release of luteinizing hormone to control ovulation. Meticulous work has identified two hypothalamic populations of kisspeptin (Kiss1) neurons that are critical for this pattern of release. The involvement of the hypothalamus is unsurprising because its quintessential function is to couple the endocrine and nervous systems, coordinating energy balance and reproduction. Estrogens, more specifically 17β-estradiol (E2), orchestrate the activity of a triumvirate of hypothalamic neurons within the arcuate nucleus (ARH) that govern the physiological underpinnings of these behavioral dynamics. Arising from a common progenitor pool, these cells differentiate into ARH kisspeptin, pro-opiomelanocortin (POMC), and agouti related peptide/neuropeptide Y (AgRP) neurons. Although the excitability of all these subpopulations is subject to genomic and rapid estrogenic regulation, Kiss1 neurons are the most sensitive, reflecting their integral function in female fertility. Based on the premise that E2 coordinates autonomic functions around reproduction, we review recent findings on how Kiss1 neurons interact with gonadotropin-releasing hormone, AgRP and POMC neurons, as well as how the rapid membrane-initiated and intracellular signaling cascades activated by E2 in these neurons are critical for control of homeostatic functions supporting reproduction. In particular, we highlight how Kiss1 and POMC neurons conspire to inhibit AgRP neurons and diminish food motivation in service of reproductive success.
AB - Pregnancy is energetically demanding and therefore, by necessity, reproduction and energy balance are inextricably linked. With insufficient or excessive energy stores a female is liable to suffer complications during pregnancy or produce unhealthy offspring. Gonadotropin-releasing hormone neurons are responsible for initiating both the pulsatile and subsequent surge release of luteinizing hormone to control ovulation. Meticulous work has identified two hypothalamic populations of kisspeptin (Kiss1) neurons that are critical for this pattern of release. The involvement of the hypothalamus is unsurprising because its quintessential function is to couple the endocrine and nervous systems, coordinating energy balance and reproduction. Estrogens, more specifically 17β-estradiol (E2), orchestrate the activity of a triumvirate of hypothalamic neurons within the arcuate nucleus (ARH) that govern the physiological underpinnings of these behavioral dynamics. Arising from a common progenitor pool, these cells differentiate into ARH kisspeptin, pro-opiomelanocortin (POMC), and agouti related peptide/neuropeptide Y (AgRP) neurons. Although the excitability of all these subpopulations is subject to genomic and rapid estrogenic regulation, Kiss1 neurons are the most sensitive, reflecting their integral function in female fertility. Based on the premise that E2 coordinates autonomic functions around reproduction, we review recent findings on how Kiss1 neurons interact with gonadotropin-releasing hormone, AgRP and POMC neurons, as well as how the rapid membrane-initiated and intracellular signaling cascades activated by E2 in these neurons are critical for control of homeostatic functions supporting reproduction. In particular, we highlight how Kiss1 and POMC neurons conspire to inhibit AgRP neurons and diminish food motivation in service of reproductive success.
KW - agouti-related peptide
KW - hypothalamus
KW - kisspeptin neurons
KW - neuropeptide Y
KW - pro-opiomelanocortin
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U2 - 10.1111/jne.13145
DO - 10.1111/jne.13145
M3 - Review article
C2 - 35581942
AN - SCOPUS:85130255171
VL - 34
JO - Journal of Neuroendocrinology
JF - Journal of Neuroendocrinology
SN - 0953-8194
IS - 6
M1 - e13145
ER -