In females FSH and LH act primarily to activate the ovaries to produce estrogen and inhibin and to regulate the menstrual cycle and ovarian cycle. For instance, the FSHβ gene exhibits ultrasensitive behavior in response to GnRH pulse frequency, with its expression sharply increasing at lower pulse frequencies and decreasing at higher frequencies. In response to GnRH stimulation these cells produce LH and FSH, which travel into the blood stream. It is known that the main targets of visfatin, as in the case of most other adipokines, are the MAPK and PI3K/Akt pathway, and the activation of Akt kinase occurs 5 min after treatment of cells with visfatin 156, 157, 158. It can be assumed that the dependence of adiponectin effect on ERK1/2 on its concentration, as well as a set of the effector components of MAPK cascade regulated by adiponectin are responsible for the different mode of the regulation of steroidogenesis by this adipokine. These data indicate that AdipoR1 plays an important role in the regulation of spermatogenesis, while AdipoR2 is very important for the T synthesis by Leydig cells. The most pronounced correlation was found between the mobility and the expression of the Adiponectin and AdipoR1 genes. The expression of the Adiponectin, AdipoR1 and AdipoR2 genes in the high-mobility spermatozoa fractions is 3.5, 3.6 and 2.5 times higher in comparison with the low-mobility fraction . The expression of the AdipoR2 gene in the testes is strongly reduced in hypophysectomized rats, and the treatment of animals with hCG completely restores it . In women, correlations may exist between positive orgasm experience and testosterone levels. Preliminary evidence suggests that low testosterone levels may be a risk factor for cognitive decline and possibly for dementia of the Alzheimer's type, a key argument in life extension medicine for the use of testosterone in anti-aging therapies. For women with PCOS, hormones like birth control pills can be used to help lessen the effects of this increased level of testosterone. The prevalence of major depressive disorder is two-folder higher in women compared to men suggesting that physiological levels of testosterone in the healthy range may reduce the risk of depression . Testosterone secreted by the testis exerts negative feedback control of hypothalamic GnRH release, while estradiol formed by 5α-reductase conversion of testosterone exerts negative feedback control of anterior pituitary luteinizing hormone (LH) secretion. Testosterone and the more biological active androgen, dihydrotestosterone (DHT), formed by conversion of testosterone by 5α-reductase, act as the primary sex hormones in men regulating male sexual development during puberty and spermatogenesis and sexual function in adulthood 1–3 (Fig. 1). The benefits of testosterone replacement therapy in men with major depressive disorder and low testosterone levels in the clinically defined hypogonadal range remain uncertain and require further investigation. Because LH drives the signal for internal testosterone production, the testes are no longer being stimulated in the same way. Suppression of LH and FSH does have real downstream effects worth understanding honestly. Certain medications, including some opioids, corticosteroids taken long-term, and anabolic steroids used outside of medical supervision, can suppress the axis. Conditions affecting the pituitary, such as a pituitary adenoma or other structural lesion, can impair the production or release of LH and FSH. Early follicles produce more androgens due to 5α-reductase activity, but dominant follicles, with high aromatase levels, shift to an estrogen-rich environment, crucial for their selection. These dimeric glycoprotein hormones, primarily produced by granulosa cells in the ovary, act as negative feedback regulators of FSH secretion from the anterior pituitary. In addition, leptin and insulin have stimulatory effects and ghrelin has inhibitory effects on gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. Defects at one or more levels of the hypothalamic-pituitary-testicular (HPT) axis can result in either primary or secondary hypogonadism. Male hypogonadism is a clinical syndrome characterized by the diminished functional activity of the testis resulting in low levels of testosterone and/or spermatozoa. In the recent years, the evidence has been obtained that leptin plays a very important role in the control of male reproductive functions and puberty, which is based on leptin-mediated regulation of the HPG axis 8, 37. The leptin-induced activation of the kisspeptin/neurokinin B/dynorphin (KNDy)-neurons leads to the secretion of kisspeptin that triggers the GnRH secretion by the GnRH-expressing neurons, the main target of kisspeptin 34, 35. The regulatory effects of leptin are realized due to its specific interaction with leptin receptors (Ob-R) that are generated by alternative splicing and include at least six isoforms . This suppression results in changes to the pulsatile release of GnRH from the hypothalamus, reverting the LH secretion pattern to pre-pubertal levels.
