Review of Medical Physiology - William F. Ganong 2002

Endocrine System, Metabolism, and Reproduction
Sex Differentiation and Development
Lactation

Development of the Mammary Glands

Full development of the mammary glands requires the coordinated action of multiple Hormones. In general, estrogens are primarily responsible for the proliferation of the mammary ducts, whereas progesterone drives lobular development. The Development of rat mammary glands during Puberty also requires a certain baseline level of prolactin, although its absolute requirement in humans remains unproven. In hypophysectomized rats, glucocorticoids, Insulin, and Growth Hormone are necessary for mammary gland development in response to other hormonal stimuli, yet by themselves they do not induce breast growth (Fig. 23-42). During Pregnancy, prolactin levels rise steadily until term; under METABOLISM/18.html">The Influence of this hormone alongside high concentrations of estrogen and progesterone, lobulo-alveolar development of the breast is completed.

Milk Secretion and Ejection

The composition of human and cow’s milk is detailed in Table 23-10. In rodents pretreated with estrogen and progesterone, the administration of prolactin triggers The formation of milk droplets and their secretion into the ducts. Oxytocin induces the contraction of myoepithelial Cells lining the ducts, facilitating the subsequent ejection of milk through the nipple (see Fig. 23-42). Reflexive milk ejection mediated by tactile stimulation of the nipples and areolae (the milk ejection reflex) is discussed in Chapter 14. In some species, though notably not in humans, oxytocin is not required for milk ejection.

Other hormonal pathways in humans are generally comparable to those in rats, although normal breast growth and lactation can still occur in dwarfs with congenital growth hormone deficiency.

The transfer of Antibodies to the newborn via colostrum is covered in Chapter 26.

Initiation of Lactation Postpartum

During pregnancy, the breasts enlarge in response to elevated circulating levels of estrogens, progesterone, prolactin, and presumably hCG. Small amounts of milk are secreted into the ducts as early as the fifth month, but this volume is negligible compared to postpartum milk secretion. In most animals, milk ejection begins within hours after delivery, whereas in women it occurs on the first to third day. Following the expulsion of the Placenta at birth, There is a sharp drop in circulating estrogen and progesterone concentrations. This decline in circulating estrogen initiates lactation. Although prolactin and estrogen act synergistically to promote breast growth, estrogen antagonizes the action of prolactin on milk production within the breast. Estrogens may be administered to women who choose not to breastfeed in order to suppress lactation.

Class="center">Table 23-10. Composition of Colostrum and Milk¹ (mass per deciliter)

¹ Reproduced with permission from Findlay ALR: Lactation. Res Reprod (Nov) 1974:6(6).

² Poor source.

Fig. 23-42. Hormonal Regulation of breast development and lactation in the rat. Estrogens (E), progesterone (P), and prolactin in the presence of glucocorticoids (G), insulin (I), and growth hormone (GH) drive ductal proliferation and growth during puberty (right). During pregnancy, these hormones ensure full alveolar development and minimal milk secretion (bottom). Postpartum, elevated prolactin release coupled with declining estrogen and progesterone levels prompt robust milk secretion and, in the presence of oxytocin, milk ejection (left). Chorionic mammotropin is a lactogenic hormone presumably secreted by the rat placenta and serves as an hCS analog, enhancing the action of prolactin.

Suckling not only triggers the reflexive release of oxytocin and milk ejection, but also sustains and increases milk secretion by stimulating prolactin release (see above).

Effects of Lactation on the Menstrual cycle

In non-nursing women, the first postpartum menses typically occurs around the sixth week. However, breastfeeding women experience Amenorrhea for 25 to 30 weeks. Lactation stimulates prolactin release, and accumulating evidence suggests that prolactin suppresses GnRH secretion, inhibits its action on the pituitary, and interferes with the effects of gonadotropins on the Ovaries. As a result, ovulation is suppressed, the ovaries remain quiescent, and estrogen and progesterone output drops. Consequently, only 5% to 10% of women conceive during the period of breastfeeding, which historically led to its recognition as an important, albeit partially effective, method of birth control. Furthermore, nearly 50% of cycles During the first six months following the resumption of menstruation are anovulatory.

Chiari-Frommel Syndrome

An intriguing though rare condition is the persistence of lactation (galactorrhea) and amenorrhea in women who do not breastfeed following childbirth. This condition, termed Chiari-Frommel syndrome, may be accompanied by genital atrophy and arises from prolonged prolactin secretion in the absence of the FSH and LH surges required for new follicular maturation and ovulation. A similar Clinical presentation of galactorrhea and amenorrhea combined with elevated circulating prolactin levels occurs in nonpregnant women with chromophobe pituitary adenomas, as well as in patients whose pituitary stalk has been transected during Cancer therapy.

Gynecomastia

Breast enlargement in males is termed gynecomastia. It can be unilateral or, more frequently, bilateral. Gynecomastia is observed in approximately 75% of newborns due to transplacental transfer of maternal estrogens. It also manifests as a mild, transient form in 70% of healthy adolescent boys during puberty and in many men over the age of 50. This condition reflects androgen resistance; it is recognized as a complication of estrogen therapy and occurs in patients with estrogen-secreting tumors. Gynecomastia is likewise associated with numerous unrelated clinical states, such as eunuchoidism, hyperthyroidism, and cirrhosis of the Liver. Digitalis administration can also induce gynecomastia because cardiac Glycosides possess weak estrogenic activity, and various other medications may trigger a similar response. The condition was notably documented in starved concentration cAMP prisoners upon liberation when adequate Nutrition was restored. A hallmark of most cases of gynecomastia is an elevated plasma estrogen-androgen ratio, driven either by an increase in circulating estrogens or a decrease in circulating androgens.

Hormones and Cancer

Approximately 35% of breast carcinomas in women of reproductive age are estrogen-dependent, meaning their continued growth relies on circulating estrogens. Tumors are not necessarily cured by suppressing estrogen production, but this intervention alleviates symptoms and induces tumor regression for months or years before relapse occurs. Women with estrogen-dependent tumors often experience remission following oophorectomy. Outcomes are more favorable if the tumor contains estrogen receptors, and even more so when both estrogen and progesterone receptors are present. Because estrogen stimulates the synthesis of progesterone receptors, their presence indicates that estrogen not only binds to but actively influences the tumor cells. Nevertheless, a subset of patients lacking these receptor types still responds to endocrine therapy. If the disease subsequently recurs, a secondary remission can sometimes be achieved by bilateral adrenalectomy. Because hypophysectomy suppresses estrogen output from both the ovaries and the Adrenal Glands, this Procedure is likewise performed in cancer patients. Additionally, evidence suggests that growth hormone and prolactin stimulate the growth of breast carcinomas, and hypophysectomy removes these driving factors.

Certain prostate carcinomas are androgen-dependent and temporarily regress following orchiectomy or Treatment with GnRH agonists administered in doses sufficient to cause down-regulation of GnRH receptors on gonadotrophs and reduced LH secretion. The development of pituitary tumors following the removal of target Endocrine glands normally regulated by pituitary trophic hormones is discussed in Chapter 22.