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FIGURE 17 Around-the-clock prolactin concentrations in eight normal women. Acute elevation of prolactin level occurs shortly after onset of sleep and begins to decrease shortly before awakening. (From Yen SC, Jaffe RB. In: Yen SC, Jaffe R, Eds., Reproductive physiology, 4th ed., Philadelphia: Saunders, 1999, p. 268. With permission.)

through several temporally distinct mechanisms. Initial inhibitory effects are detectable within seconds and result from membrane hyperpolarization, which deactivates voltage-sensitive calcium channels and lowers intracellu-lar calcium. This effect appears to result from direct stimulation of potassium influx by G-protein-gated channels. Minutes later there is a decrease in cAMP which leads to decreased transcription of the prolactin gene. Estrogens are thought to decrease responsiveness to dopamine by uncoupling dopamine receptors from G proteins. On a longer time scale, dopamine antagonizes the proliferative effects of estrogen by mechanisms that are not understood.

Prolactin in Blood

Prolactin is secreted continuously at low basal rates throughout life, regardless of sex. Its concentration in blood increases during nocturnal sleep in a diurnal rhythmic pattern. Basal values are somewhat higher in women than in men and prepubertal children, presumably reflecting the effects of estrogens. Episodic increases in response to eating and stress are superimposed on this basal pattern (Fig. 17). Prolactin concentrations rise steadily in maternal blood throughout pregnancy to about 20 times the nonpregnant value (Fig. 18). After delivery, prolactin concentrations remain elevated, even in the absence of suckling, and slowly return to the prepregnancy range, usually within less than 2 weeks. Prolactin also increases in fetal blood as pregnancy progresses, and during the final weeks reaches levels that are higher than those seen in maternal plasma. The fetal kidney apparently excretes prolactin into the amniotic fluid where at midpregnancy the prolactin concentration is five to ten times higher than that of either maternal or fetal blood. Although some of the prolactin in maternal

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