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In the last decade, several studies elucidating specific roles of LH and hCG were published and reviewed3,155–157, pinpointing the differences between the two gonadotropins. Receptor bound to the hormone is internalized via different kinds of endosomal compartments, sustaining prolonged signaling, receptor degradation, or recycling on the cell surface. A gonadotropin receptor recycling pathway involves a novel intracellular compartment, the very-early endosome (VEE), where LHCGR is routed through the interaction of the so-called "Gαi-interacting protein C-terminus" (GIPC) with the PDZ protein binding domain100. In this case, a crucial role is played by a palmitoylated cysteine at the C-tail, which is required for maintaining proper FSHR recycling, preventing excessive degradation and, likely, impairment of the cell signaling143. For instance, perturbation of RAB5- or the clathrin-binding protein (DENND1A)-encoding gene expression in theca cells may result in over-activation of androgen synthesis and subsequent increased susceptibility to the disease141.
Gonadotropins are essential to your reproductive health. FSH and LH are gonadotropins (goh-NA-doh-TROH-pinz). The androgen replacement modality used for treatment of hypogonadal males with absent or reduced endogenous LH/FSH secretion may impact on long-term health and quality of life. 17-OH-pregnenolone, androstenedione and DHEAS (Δ5 pathway), three 11-oxygenated C19 androgens (11-keto-A4, 11-keto-T and 11-keto-DHT) and the testosterone (T) metabolites DHT and 17ß-oestradiol (E2) were similar to controls. Androstanediol, a marker of the backdoor pathway of dihydrotestosterone (DHT) synthesis, was increased.
Even though the aromatase complex is required for estrogen synthesis, its biological relevance is also related to the regulation of the balance between androgens and estrogens in different tissues. ERβ expression was detected mostly in spermatogonia, primary spermatocytes, and immature spermatids. The estradiol-binding protein GPER1 also mediates estrogen action in target tissues.
Progesterone is necessary for maintenance of pregnancy, and, in most mammals, LH is required for continued development and function of corpora lutea. In females, ovulation of mature follicles on the ovary is induced by a large burst of LH secretion known as the preovulatory LH surge. Together, they regulate many aspects of gonadal function in both males and females. As described for thyroid-simulating hormone, LH and FSH are large glycoproteins composed of alpha and beta subunits. Reproductive endocrinologists undergo extensive medical training, first in a four-year residency in obstetrics and gynecology, then in a three-year fellowship in reproductive endocrinology.
Activin signals are activated through interaction with specific receptors that belong to a serine/threonine kinase family and activate intracellular Smad proteins . Predominant in primates, inhibin B is more abundant in adult serum compared to inhibin A. It controls DNA synthesis and meiotic chromosome dynamics through the regulation of activin A, inhibin B, IL-6, and nociception, thus promoting spermatocytes to enter meiosis 88,89,90. Furthermore, signaling enhances SSC differentiation through the activation of key factors such as stem cell factor (SCF), steel factor (SLF), bone morphogenetic protein-4 (BMP4), and insulin-like growth factor 3 (IGF3) 51,86,87. For example, transcription factors including Krüppel-like factor 4 (KLF4) , nuclear factor (NF)-κB , and activator protein-1 (AP-1) are involved in the regulation of Sertoli cell differentiation by FSH. Furthermore, FSH targets functional factors and transcription factors through the cAMP/PKA pathway to affect Sertoli cell differentiation and apoptosis 76,77. FSH-induced signal transduction is mediated by FSHR, and its function reliant on interactions with numerous intracellular effectors.
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