Endocrinology
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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. ⋯ 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.
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Most organisms, including humans, have developed an intrinsic system of circadian oscillators, allowing the anticipation of events related to the rotation of Earth around its own axis. The mammalian circadian timing system orchestrates nearly all aspects of physiology and behavior. ⋯ There is increasing evidence on the essential roles of the peripheral oscillators, operative in metabolically active organs in the regulation of body glucose homeostasis. Here, we review some recent findings on the molecular and cellular makeup of the circadian timing system and its implications in the temporal coordination of metabolism in health and disease.
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The postnatal synchronization of the circadian variation of the adrenal clock genes in mammals remains unknown. We evaluated the postnatal ontogeny of daily variation of clock genes (Clock/Bmal1/Per1/Per2/Per3/Cry1/Cry2/Rorα/Rev-Erbα) and steroidogenesis-related genes (Star and Mc2r) in rat adrenals and its relationship with the emergence of plasma corticosterone rhythm using cosinor analysis. Plasma corticosterone circadian rhythm was detected from postnatal day (P)1, with morning acrophase, between zeitgeber time (ZT)0 and ZT2. ⋯ In all postnatal ages, Per2 and Cry1 circadian profiles were synchronized in phase with the circadian rhythm of plasma corticosterone, whereas Bmal1 was in antiphase. An adult-like Star circadian rhythm profile was observed only from P21. In conclusion, our original data demonstrated a progressive postnatal maturation of the circadian variation of the adrenal clock genes in synchrony with the development of the corticosterone circadian rhythm in rats.
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The hypothesis that phosphorylation of progesterone receptor (PR) isoforms, PR-A and PR-B, in myometrial cells affects progesterone action in the context of human parturition was tested. Immunodetection of phosphoserine (pSer) PR forms in term myometrium revealed that the onset of labor is associated with increased phosphorylation of PR-A at serine-345 (pSer345-PRA) and that pSer345-PRA localized to the nucleus of myometrial cells. In explant cultures of term myometrium generation of pSer345-PRA was induced by interleukin-1β and dependent on progesterone, suggesting that pSer345-PRA generation is induced by a proinflammatory stimulus. ⋯ Taken together, the data show that human parturition involves the phosphorylation of PR-A at serine-345 in myometrial cells and that this process is ligand dependent and induced by a proinflammatory stimulus. We also found that in myometrial cells, pSer345 activates the capacity for PR-A to inhibit antiinflammatory actions of progesterone mediated by PR-B. Phosphorylation of PR-A at serine-345 may be an important functional link between tissue-level inflammation and PR-A-mediated functional progesterone withdrawal to trigger parturition.
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Several trigeminal pain disorders show sex differences, and high levels of estrogens may underlie these differences. The interaction between transient receptor potential vanilloid 1 (TRPV1) and anoctamin 1 (ANO1) plays an important role in peripheral nociception. However, whether TRPV1 and ANO1 are involved in estrogen-modulated trigeminal pain sensitivity is unclear. ⋯ The number of c-Fos-immunoreactive cells in the ventral trigeminal interpolaris/caudalis were similar in the 2 groups. Real-time PCR showed that the levels of TRPV1 and ANO1 mRNA in the HE group were significantly higher than levels in the LE group. Thus, high levels of estrogens may be a risk factor for Cap-evoked nociceptive pain, and estrogen-dependent increases in TRPV1 and ANO1 are likely involved in modulating the nociceptive response in the trigeminal area.