Review of Medical Physiology - William F. Ganong 2002

Endocrine System, Metabolism, and Reproductive Function
Sexual Differentiation and Development
Pituitary Gonadotropins and Prolactin

Chemical Structure

Both FSH and LH consist of α- and β-subunits, The structure of which is described in Chapter 22. They are Glycoproteins containing hexoses (mannose and galactose), hexosamines (N-acetylgalactosamine and N-acetylglucosamine), methylpentose fucose, and sialic acid. CARBOHYDRATES in gonadotropin molecules enhance their activity by noticeably slowing down their METABOLISM. The half-life of human FSH is 170 min, and that of LH is approximately 60 min. Confirmed Mutations in the FSH β-subunit are now identified in men with hypogonadism and in women with delayed Puberty and hypogonadism.

Human pituitary prolactin consists of 199 amino acid residues, three disulfide bridges (Fig. 23-14), and bears a striking structural resemblance to human Growth Hormone and HPL. The half-life of prolactin, much like that of growth hormone, is 20 min. Structurally similar prolactins are also secreted by the endometrium and Placenta (see below).

Receptors

FSH and LH receptors are serpentine receptors that couple to adenylate cyclase via a G_S PROTEIN (see Chapter 1). In addition, each possesses an extended, glycosylated extracellular domain.

The human prolactin receptor is structurally similar to the growth hormone receptor, belonging to a receptor superfamily that includes the growth hormone receptor as well as receptors for numerous cytokines and hematopoietic growth factors (see Chapters 1, 22, 24, and 27). It dimerizes and activates JAK-Stat and other intracellular enzyme cascades.

Action

The Testes and Ovaries undergo atrophy following hypophysectomy or pituitary destruction. The effects of prolactin and the gonadotropins FSH and LH, as well as placental gonadotropins, are described in detail below. Here, It is worth noting only that FSH maintains the spermatogenic epithelium by stimulating Sertoli Cells in males and drives early follicular growth in the ovaries of females. LH is tropic to Leydig cells and, in females, is responsible for the final maturation of ovarian follicles, estrogen secretion, ovulation, initial Formation of the corpus luteum, and progesterone release.

Prolactin induces milk secretion from the Mammary Glands following estrogen and progesterone priming. It acts on the mammary gland by enhancing mRNA activity and increasing The production of casein and lactalbumin. However, the hormone's action does not extend to The Cell nuclei, a process prevented by microtubule inhibitors. Prolactin also suppresses gonadotropin action, likely at the ovarian level. Its significance in preventing ovulation in lactating women is discussed below. The function of prolactin in healthy males is not yet fully understood, although hyperprolactinemia caused by tumors results in impotence. Prolactin, used as a standard for quantifying the biological activity of this hormone, stimulates the GROWTH AND DEVELOPMENT of a "secretory" crop in pigeons and other birds. The paired crops are esophageal outpouches where desquamation of the inner lining cells produces a nutrient product ("crop milk") used by birds to feed their offspring. Prolactin, FSH, and LH are determined by radioimmunoassay.

Regulation of Prolactin Secretion

Under normal conditions, plasma prolactin concentrations are approximately 5 ng/mL in men and 8 ng/mL in women. Its secretion is tonically inhibited by the Hypothalamus, and sectioning of the pituitary stalk leads to elevated circulating prolactin levels. The Influence of the hypothalamic hormone dopamine, which inhibits prolactin secretion (prolactin-inhibiting hormone - PIH), normally overrides that of various hypothalamic Proteins possessing prolactin-releasing activity. In humans, prolactin secretion increases in response to exercise, surgical and psychological stress, and nipple stimulation (Table 23-3). Plasma prolactin levels rise during Sleep, beginning at sleep onset and persisting until awakening. Its secretion also increases progressively throughout Pregnancy, peaking at parturition. Within eight days postpartum, plasma concentrations decline to pre-pregnancy levels. Breastfeeding triggers a transient surge in prolactin release, though baseline levels gradually decline after three months of Lactation. As lactation continues, prolactin levels return to normal.

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Fig. 23-14. Structure of human prolactin.

L-DOPA decreases prolactin release by increasing dopamine formation, whereas bromocriptine and other dopamine agonists inhibit this process through The stimulation of dopamine receptors. Chlorpromazine and other drugs that block dopamine receptors promote increased prolactin release. TRH stimulates prolactin release along with TSH, and additional prolactin-releasing Polypeptides are present in hypothalamic tissue. Estrogens promote a slow increase in prolactin release through a direct action on lactotrophs.

It has been established that prolactin facilitates dopamine release in the median eminence. Consequently, prolactin acts within the hypothalamus to inhibit its own secretion via a negative feedback mechanism.

Hyperprolactinemia

Up to 70% of patients with a chromophobe Adenoma of the anterior pituitary have elevated plasma prolactin levels. In some cases, the elevation is caused by pituitary stalk lesions, but more frequently the tumor cells themselves secrete the hormone. Hyperprolactinemia can cause galactorrhea, although the majority of individuals exhibit no signs of endocrine disorders. Conversely, most women with galactorrhea have normal prolactin concentrations. Actual elevation of prolactin is detected in less than a third of patients presenting with this condition.

Table 23-3. Factors Affecting Prolactin and Growth Hormone Secretion in Humans

¹ I - moderately increased; I+ - markedly increased; I++ - massively increased; U - unchanged; D - moderately decreased; D+ - markedly decreased.

Another interesting finding is that 15% to 20% of women with secondary Amenorrhea have elevated prolactin levels; furthermore, when prolactin release is reduced, normal menstrual cycles and fertility are restored. Prolactin may also induce amenorrhea by blocking the action of gonadotropins on the ovaries, although this mechanism is not yet fully understood. Hypogonadism caused by prolactinomas is associated with Osteoporosis resulting from estrogen deficiency.

As noted above, hyperprolactinemia in men is associated with impotence and hypogonadism, both of which resolve when prolactin release is reduced.