Hypothalamic-pituitary-gonadal axis

Thomas EJ, Walton PL, Thomas NM, Dowsett M (1994) The effects of ICI 182,780, a pure anti-oestrogen, on the hypothalamic- pituitary-gonadal axis and on endometrial proliferation in pre- menopausal women. Hum Reprod 9 1991-1996... 

There has been some concern that the recently observed decline in sperm quality may be related to exposure to environmental estrogens (Sharpe and Skakkebaek, 1993) and at the same time there has been speculation that these estrogenic compounds may exert inhibitory effects against prostate cancer (Kurzer, 2002). Theoretically, exposure to high levels of dietary estrogens could alter the hypothalamic-pituitary-gonadal axis in men, but dietary studies to date have not shown such an hormonal effects. 

Figure 17.2 The hypothalamic-pituitary-gonadal axis. Endocrine signaling cascades provide multiple sites for regulation and ensure optimum signaling.

Figure 20.1 Hypothalamic-pituitary-gonadal axis. Negative feedback is designated by (—), and positive feedback is designated by (+).

Rivier C, Rivest S. Effect of stress on the activity of the hypothalamic-pituitary-gonadal axis peripheral and central mechanisms. Biol Reprod 1991 45 523-532. 

Fig. 1. Hormone secretion and control of the hypothalamic-pituitary-gonadal axis. Plus and minus signs indicate stimulation and inhibition respectively. In both male and female animals the dominant feedback effect of gonadal steroids on the hypothalamic-pituitary axis is inhibitory. The only major exception is in the female in which a rapid FSH-induced increase in the concentration of oestradiol triggers a large increase of the secretion of LH to induce ovulation. Note that LHRH secreted by the hypothalamus is carried directly to the pituitary gland without entering the peripheral circulation. Since the pituitary and gonadal hormones are secreted into the peripheral blood stream the functional response to hormone agonists or antagonists may be assessed by simple measurements of circulating hormone concentration ).

In terms of pharmacological management, often little can be done for those with an abnormality in the hypothalamic-pituitary-gonad axis. In some patients hormone replacement is required, and in patients with Turner s syndrome in vitro fertilization and hormone therapy can be offered. 

In prospective non-randomized non-blinded evaluation of the effects of a 12-week course of intrathecal opioids for the control of chronic non-cancer pain on the hypothalamic-pituitary-gonadal axis in 12 men, it was suppressed and serum testosterone concentrations fell (44). This effect not only reduces quality of life through sexual... 

Cicero TJ, Badger TM. 1977. Effects of alcohol on the hypothalamic-pituitary-gonadal axis in the male rat. J. Pharmacol. Exp. Ther. 201 427-33... 

Figure 50-9 The regulatory feedback loop of the hypothalamic-pituitary-gonadal axis. Neural and sensory input from the brain elicits the release of Gn-RH. Gn-RH in turn stimulates the synthesis and release of the gonadotropins FSH and LH, which act on the gonads (ovary and testes) to elicit the ripening and ovulation of the ovary and steroidogenesis (estradiol and progesterone) in the female and spermatogenesis and testosterone production in the male. Inhibin formed by the ovaries and testes along with estradiol and testosterone negatively feeds back to the hypothalamic-pituitary axis to modulate Gn-RH, FSH, and LH release.

Concentrations of androstenedione, DHEA, and DHEA-S begin to increase as early as 6 to 7 years of age, several years before maturation of the hypothalamic-pituitary-gonadal axis. The onset of puberty is associated with nocturnal surges in LH and, to a lesser extent, FSH secretion. The overall changes associated with puberty reflect the theory that the hypothalamic-pituitary system becomes less sensitive to feedback inhibition by circulating androgens, resulting in... 

Precocious puberty is classified as GuRH dependent or independent. GnRH-dependent precocious puberty (also called central precocious puberty) is due to precocious activation of the hypothalamic-pituitary-gonadal axis. In girls, the cause is most commonly idiopathic (90%) however, idiopathic cases account for less than 10% of central precocious puberty in boys. Central nervous systeni tumors can also cause central precocious puberty, the most common being hypothalamic hamartomas. Neurofibromatosis has been also reported to lead to GnRH-dependent precocious puberty. 

Infertility problems often arise as a result of hormonal dysfunction of the hypothalamic-pituitary-gonadal axis. Measurement of peptide and steroid hormones in the serum is therefore an essential aspect of the evaluation of infertility. This section focuses on the hormonal and biochemical aspects of evaluating infertility. 

Veldhuis JD. The male hypothalamic-pituitary-gonadal axis. In Yen SSC, Jaffe RB, Barbieri RL, eds. Reproductive endocrinology Physiology, pathophysiology, and chnical management. 4th ed. Philadelphia WB Saunders Co, 1999 622-31. 

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