The Endocrinology of Mammalian Reproduction

Abstract The reproductive system includes the HPG axis and sex accessory structures. Primary control resides in pulsatile production of GnRH, which controls pituitary production of FSH and LH, which in turn cause gamete formation, gonadal steroid secretion, and regulation of sexual characters and reproductive behaviors. FSH is involved primarily with gamete production whereas LH is responsible for initiating steroid secretion and release of mature gametes (ovulation and spermiation). FSH and testosterone work cooperatively to produce mature sperm. Sex steroids stimulate other primary reproductive structures and secondary sex characters as well as mating behavior In mammals, the male sex is determined by the sry gene, which is responsible for production of AMH and androgens by the testis. AMH causes regression of some potential female structures and androgen production allows development of male sex accessory structures and reprograms hypothalamic reproductive centers in the brain to the male secretory pattern. The default sex in mammals is female although a number of transcription factors and nuclear receptor proteins are required for ovary development and estrogens are essential for completely normal female development. Mammalian reproductive cycles show great variations. Monotremes are egg-laying mammals that nourish their hatchlings with milk from their mammary glands. Marsupials allow their young to develop in a pouch after a short gestation period involving a nonendocrine placenta, relying on the mammary glands to support continued development of an exteriorized fetus. Eutherian mammals have a prolonged period of intrauterine fetal development supported by an endocrine placenta. Mammary glands are used for nutritional support after birth in all mammals. Most female mammals exhibit an ovarian-based estrous cycle characterized by a period of enhanced receptivity of the female to the male called estrus. In some species a special phase of the uterine cycle occurs, the menses, which involves sloughing and discharge of a portion of the endometrium and trapped blood. Because of this special uterine cycle, their reproductive cycles are typically called menstrual cycles and most may (e.g., rhesus monkey) or may not (human) exhibit a distinct period of estrus. The proliferative phase of the uterine cycle corresponds closely to the follicular phase of the ovarian cycle, and the secretory phase of the uterine cycle that follows ovulation coincides exactly with the luteral phase of the ovarian cycle. The uterine secretory phase is followed by a quiescent phase called diestrus in most mammals or by the menses in species having a uterine menstrual cycle. The menses corresponds to the first few days of the next follicular phase in the ovary. In eutherians, the cycle can be separated into a follicular phase during which one or more ova develop in follicles and a luteal phase that prepares the uterus for implantation of the blastocyst. The luteal phase is named for one or more corpora lutea that develop from ruptured follicles and possibly some atretic follicles that continue to secrete estrogens and progestogens. During pregnancy, the eutherian placenta in cooperation with the fetal adrenal functions as an endocrine gland to maintain pregnancy, initiate birth, and prepare the mammary glands for postnatal functions. The corpus luteum performs various roles in pregnancy depending on the species. Postnatal functions of the mammary gland are controlled by PRL and OXY from the pituitary gland. Gonadal secretory activities involve two special cell types responsive to FSH and LH, respectively. Ovarian granulosa cells and testicular Leydig cells are responsive primarily to LH and synthesize androgens. Ovarian thecal cells and testicular Sertoli cells as well as Leydig cells respond to FSH with conversion of androgens into estrogens . FSH also stimulates Sertoli cells . Gonadal cells make many other local regulators in response to GTHs or independently, and these regulators may have autocrine and/or paracrine actions that control local events in the gonads.