The major role exerted by estrogen has been recently demonstrated in some physiopathological conditions since estriol administration was able to induce a greater response of gonadotrope cells to both exogenous and endogenous GnRH stimulation. Obviously, gonadal steroids also play a crucial role in the modulation of the GnRH-induced gonadotropin secretion, since estrogen and androgens are able to greatly interfere in the amount of LH released from the pituitary through the feedback control system.
All of them can interfere in the regulation of GnRH, thus influencing the reproductive capacity overall. Stressful situations such as psychological, physical or metabolic stressors, together with weight fluctuations, such as loss of weight or obesity, can induce an impaired neuroendocrine function at the hypothalamic level through the impaired production of amines, beta-endorphin, and serotonin. In fact, a number of neuropeptides and neurotransmitters released inside the central nervous system (CNS) act on the modulation of the release of GnRH, thus affecting the reproductive functions. Therefore, also all these modulators of kisspeptin and GnRH release indirectly affect the release of gonadotropins. As for many neuroendocrine systems, kisspeptin is extremely sensitive to the many signal coming from the periphery-mainly metabolic signals such as Ghrelin, cholecystokinin, leptin and insulin-and it greatly affected by changes coming from the gastro-intestinal tract. The biggest driving force of GnRH discharge is kisspeptin, whose receptors are expressed on GnRH neurons. The whole reproductive system depends on GnRH neurons’ secretory activity and around the receptors expression, which are modulated by positive and negative factors so as to activate or impair their functions.
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