Mechanisms of Endocrine System Function

Abstract

HORMONAL AXES 31disruptors are able to disturb hormonal homeostasis of organisms by mimicking the hormonal activity of the natural hormones.The lipophilic steroid and thyroid hormones (THs) simply diffuse across the plasma membrane and out of the cell down a concentration gradient to readily enter cells to interact with cytoplasmic or nuclear receptors. Hypothalamus-Pituitary-Gonad (HPG) AxisThe primary function of the HPG axis in vertebrates is to facilitate the production of germ cells in males and to coordinate reproductive events such as ovulation, pregnancy, and lactation in females. In addition to its function in adult animals, the HPG axis regulates the differentiation of the sex-specific phenotype during early development, where sex steroids play a pivotal role.The hypothalamus, located at the base of the brain, acts as a central processor for regulating the endocrine system by maintaining homeostasis of a variety of physiologic functions. It initiates the secretion of gonadotropin-releasing hormone (GnRH) in a pulsatile manner into the blood. At the anterior pituitary, the GnRH diffuses to its target cells, called gonadotropes. The gonadotrope cells synthesize/secrete the gonadotropins, LH, and FSH. In response to GnRH stimulation, the gonadotropes quickly release the gonadotropins from the pituitary gland into the general circulating system, and target the gonads (ovary or testis). At the gonad, gonadotropins drive the synthesis of steroid hormones via steroidogenesis and production of sperm and ova via gametogenesis. Sertoli and Leydig (testis) cells and theca and granulosa (ovary) cells have receptors for LH and FSH, and produce steroid hormones including estrogen and testosterone, as well as other factors (such as inhibin B), which induce a direct effect on hormone-responsive tissues. The steroid hormones, in turn, regulate GnRH production in the hypothalamus (and, therefore, secretion of pituitary gonadotropins). The hypothalamus and pituitary operate under negative feedback control regulated by levels of gonadotropins and steroids. This control route, hypothalamus → pituitary → gonad, is called the HPG axis ( Fig. 2.2), and is one of several highly conserved hypothalamic-pituitary-hormonal axes in the vertebrates.During puberty, the HPG axis is activated, leading to increases in LH, FSH, and sex steroids (testosterone and estradiol) levels (Grumbach and Styne, 2003). LH and FSH play important roles in the menstrual cycle. LH stimulates production of testosterone from Leydig cells and secretion by the follicle. FSH stimulates the Sertoli cells, causing the testes to produce a hormone that regulates sperm production. Sex steroids then act upon steroid hormone receptors, primarily estrogen receptors (ERs), androgen receptors (ARs), and progesterone receptors (PRs), that are widely expressed in target tissues, including the reproductive tract and genitalia, breast, and other organ systems.Under the control of FSH, androgen is converted to estrogen by aromatizing the A ring of the steroid molecule throu...