Sex Differences in Steroid Receptor Coexpression and Circadian-Timed Activation of Kisspeptin and RFRP-3 Neurons May Contribute to the Sexually Dimorphic Basis of the LH Surge.
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The identified sex differences in absolute and CT‐dependent AVPV Kiss1 levels, AVPVs sex steroid receptor levels, and circadian‐timed changes in neuronal activation of both Kiss1 and Rfrp neurons suggest that multiple sexually dimorphic processes in the brain may underlie proper LH surge generation.Abstract:
In rodents, the ovulation-inducing luteinizing hormone (LH) surge is sexually dimorphic, occurring only in females, but the reasons for this sex difference are unclear. Two neuropeptides, kisspeptin and RFamide-related peptide 3 (RFRP-3), are hypothesized to regulate the gonadotropin-releasing hormone (GnRH)/LH surge. In females, both of these systems show circadian changes coincident with the LH surge, but whether males show similar temporal changes under comparable hormonal conditions is unknown. Here, we evaluated circadian time (CT)-dependent changes in gene expression and neuronal activation of Kiss1 and Rfrp neurons of female and male mice given identical LH surge-inducing estrogen regimens. As expected, females, but not males, displayed a late afternoon LH surge and GnRH neuronal activation. Kiss1 expression in the anteroventral periventricular nucleus (AVPV) was temporally increased in females in the late afternoon, whereas males demonstrated no temporal changes in AVPV Kiss1 expression. Likewise, neuronal activation of AVPV Kiss1 neurons was dramatically elevated in the late afternoon in females but was low at all circadian times in males. Estrogen receptor α levels in AVPV Kiss1 neurons were sexually dimorphic, being higher in females than males. AVPV progesterone receptor levels were also higher in females than males. Hypothalamic Rfrp messenger RNA levels showed no CT-dependent changes in either sex. However, Rfrp neuronal activation was temporally diminished in the afternoon/evening in females but not males. Collectively, the identified sex differences in absolute and CT-dependent AVPV Kiss1 levels, AVPV sex steroid receptor levels, and circadian-timed changes in neuronal activation of both Kiss1 and Rfrp neurons suggest that multiple sexually dimorphic processes in the brain may underlie proper LH surge generation.read more
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Journal ArticleDOI
Dominant Neuropeptide Cotransmission in Kisspeptin-GABA Regulation of GnRH Neuron Firing Driving Ovulation.
Richard Piet,Bruna Kalil,Timothy McLennan,Robert Porteous,Katja Czieselsky,Allan E. Herbison +5 more
TL;DR: Evidence is provided that an RP3V neuron population coexpressing kisspeptin and GABA provides a functionally important excitatory input to GnRH neurons at the time of ovulation.
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Hyperactive LH Pulses and Elevated Kisspeptin and NKB Gene Expression in the Arcuate Nucleus of a PCOS Mouse Model.
TL;DR: The findings indicate that LET mice, like PCOS women, have markedly elevated LH pulsatility which likely drives increased androgen secretion in LET PCOS-like condition.
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Circadian regulation of endocrine systems.
TL;DR: The rhythmicity of endocrine axis formation has important functions for the maintenance of homeostasis and stabilizes physiological functions against external perturbations and may affect the function of the circadian clock network to alter further downstream processes.
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Functional Implications of RFRP-3 in the Central Control of Daily and Seasonal Rhythms in Reproduction.
Eleni Angelopoulou,Eleni Angelopoulou,Clarisse Quignon,Lance J. Kriegsfeld,Valérie Simonneaux +4 more
TL;DR: The goal of this review is to survey the current understanding of the role played by RFRP-3 in the temporal regulation of reproduction, and consider how its effect might combine with that of kisspeptin to improve the synchronization of reproduction to environmental challenges.
Journal ArticleDOI
Sex differences in steroid levels and steroidogenesis in the nervous system: Physiopathological role.
Silvia Giatti,Silvia Diviccaro,Melania Maria Serafini,Donatella Caruso,Luis M. Garcia-Segura,Barbara Viviani,Roberto Cosimo Melcangi +6 more
TL;DR: The state of the art of neuroactive steroids, particularly taking in consideration sex differences occurring in the synthesis and levels of these molecules are summarized.
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Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54
Sophie Messager,Emmanouella E. Chatzidaki,Dan Ma,Alan G. Hendrick,Dirk Zahn,John Dixon,Rosemary R. Thresher,Isabelle Malinge,Didier Lomet,Mark B. L. Carlton,William H. Colledge,Alain Caraty,Samuel Aparicio +12 more
TL;DR: GPR54 is defined as a major control point in the reproductive axis and kisspeptin is suggested to be a neurohormonal effector, demonstrating that a key action ofkisspeptin on the hypothalamo-pituitary-gonadal axis occurs directly at the level of GnRH release.