The Interplay between Circadian System, Cholesterol Synthesis, and Steroidogenesis Affects Various Aspects of Female Reproduction

Abstract

Circadian aspect of reproduction has gained much attention in recent years. In mammals, it is very important that the timing of greatest sexual motivation is in line with the highest fertility. Peripheral clocks have been found to reside also in reproductive organs, such as the uterus and ovary. The timing signal from the suprachiasmatic nucleus is suggested to be transmitted via hormonal and neural mechanisms, and could thus mediate circadian expression of target genes in these organs. In turn, estrogens from the ovary have been found to signal back to the hypothalamus, completing the feedback loop. In this review we will focus on the interplay between clock and estrogens. Estradiol has been directly linked with expression of Per1 and Per2 in the uterus. CLOCK, on the other hand, has been shown to alter estradiol signaling. We also present the idea that cholesterol could play a vital role in the regulation of reproduction. Cholesterol synthesis itself is circadially regulated and has been found to interfere with steroidogenesis in the ovary on the molecular level. This review presents a systems view on how the interplay between circadian clock, steroidogenesis, and cholesterol synthesis affect various aspects of mammalian reproduction.

Breast cancer risk, nightwork, and circadian clock gene polymorphisms

“…It has been demonstrated that sex hormones may influence the expression of circadian genes (Nakamura et al 2001, Mostafaie et al 2009) and that circadian genes may play a role in hormone regulation (Urlep & Rozman 2013). Although, the exact mechanisms underlying this interplay are largely unknown, the differences we observed between post-and premenopausal women may be explained in part by differences in circulating levels of estrogen and progesterone in these two groups.…”

Evidence for clock genes circadian rhythms in human full-term placenta

“…It is accepted that a large variety of physiological functions, including reproductive processes, metabolism, and hormone secretions, depend on the circadian clock [Miller et al 2004;Urlep and Rozman 2013]. But circadian peripheral disruption increases disease risk.…”

Neuroendocrine underpinnings of sex differences in circadian timing systems

“…The key neuroendocrine cell populations involved in this event are those containing gonadotropin inhibiting hormone (GnIH), gonadotropic releasing hormone (GnRH) and kisspeptin (Kiss1). These neurosecretory cells receive monosynaptic projections from the SCN, but studies of these pathways have focused on females, with a dearth of evidence in males [27, 38] (Fig. 3).…”

“…Neurons in the core SCN containing vasoactive intestinal peptide project directly to GnRH neurons in the medial preoptic area (MPOA), while those in the shell SCN containing vasopressin project to Kiss1 neurons in the anteroventral paraventricular nucleus (AVPV) [38]. Although the neuropeptidergic phenotype remains to be discovered, direct projection from the SCN to GnIH neurons in the dorsomedial hypothalamus (DMH) has been reported [39].…”