Updates on molecular and environmental determinants of luteal progesterone production

Abstract

Progesterone, a critical hormone in reproduction, is a key sex steroid in the establishment and maintenance of early pregnancy and serves as an intermediary for synthesis of other steroid hormones. Progesterone production from the corpus luteum is a tightly regulated process which is stimulated and maintained by multiple factors, both systemic and local. Multiple regulatory systems, including classic mediators of gonadotropin stimulation such as the cAMP/PKA pathway and TGFβ-mediated signaling pathways, as well as local production of hormonal factors, exist to promote granulosa cell function and physiological fine-tuning of progesterone levels. In this manuscript, we provide an updated narrative review of the known mediators of human luteal progesterone and highlight new observations regarding this important process, focusing on studies published within the last five years. We will also review recent evidence suggesting that this complex system of progesterone production is sensitive to disruption by exogenous environmental chemicals that can mimic or interfere with the activities of endogenous hormones.

Hand2os1 Regulates the Secretion of Progesterone in Mice Corpus Luteum

“…This suggests that Hand2os1 has no significant effect on CL formation and degeneration. P 4 is a key reproductive hormone in the establishment and maintenance of early pregnancy, and its synthesis is regulated by many factors [4]. Some lncRNAs, such as SRA, H19, and Neat1, also play a role in the production of steroid hormones and the expression of key enzymes [12,31,32].…”

“…This result suggests that Hand2os1 may be involved in the secretion of P 4 in LCs. StAR and Cyp11a1 are key enzymes in progesterone synthesis [4]. We inhibited Hand2os1 with a specific siRNA and reduced the expression of the key steroid genes StAR and Cyp11a1.…”

“…Luteal cells utilize steroidogenic acute regulatory protein (StAR), P450 cholesterol side chain cleavage enzyme (P450scc; encoded by CYP11A1), and 3β-hydroxysteroid dehydrogenase (3β-HSD) to produce progesterone, and this process is regulated tightly. [4]. Ovulation occurs with a sudden increase in luteinizing hormone (LH) levels, followed by luteinization of the granulosa cells (GC), where StAR expression increases.…”

“…P450scc then catalyzes the conversion of cholesterol to pregnenolone, which is further metabolized to progesterone via 3β-HSD. [4][5][6].…”