Plc

Gpic

Stimulation Uterus, CNS

" Abbreviations are the same as those in the legend of Fig. 4-18.

" Abbreviations are the same as those in the legend of Fig. 4-18.

transcription-translation. Norepinephrine levels are elevated in the dorsal septal nucleus and in the supraoptic nucleus compared to those in homozygous nondiabetic rats. Catecholamine levels are lower in the paraventricular nucleus of the diabetic rats compared to those in controls. These results and other studies suggest that VP modulates catecholamine neurotransmission in specific brain regions and may be related to the effects of VP on behavior, learning, and memory.

H. Overview of Regulation of Oxytocin Secretion from the Posterior Pituitary

A summary of the secretion of OT from the posterior pituitary is shown in Figure 4-19. Two major functions are milk ejection in lactating females and participation in signaling uterine contractions at the termination of pregnancy. Some experiments suggest that OT may cause the inhibition of androgen synthesis in the testis, but knowledge of the regulation of secretion of OT in males is not clear. Suckling and related stimuli (audi tory, visual) result in milk ejection from the mammary gland of nursing females and are transmitted rapidly over a spinal reflex arc to the paraventricular nucleus of the hypothalamus (see also Chapter 14). This stimulus appears to be cholinergic and is transmitted to nerve endings in the posterior pituitary, resulting in Ca2+ uptake, depolarization, and exocytosis of OT-NP into circulation. The OT-NP complex is dissociated after exocytosis.

Transmission of the suckling stimulus to the paraventricular nucleus of the hypothalamus by way of a spinal arc reflex is accomplished in milliseconds. The oxytocinergic neuron is stimulated by acetylcholine and repressed by norepinephrine; thus, it can be envisioned as being positively regulated by a cholinergic interneuron and negatively regulated by an adrenergic interneuron. Visual stimuli (e.g., the sight of a hungry infant or auditory stimuli such at the sound of a baby's cry) can lead to dripping of milk from the breast. These signals are transmitted to the hypothalamus and result in the release of some OT. On the other hand, fear and

Paraventricular nucleus of hypothalamus

High progesterone Neurohypophysis nerve

Paraventricular nucleus of hypothalamus

High progesterone Neurohypophysis nerve

FIGURE 4-19 Secretion of OT from the posterior pituitary. The effect of OT in the testis appears to lower androgen levels and elevate pregnenolone and progesterone.

4. Posterior Pituitary Hormones stress can inhibit OT release. Only a few seconds are required for OT to reach its target in the mammary gland. After dissociation of the NP, OT binds to a specific cell membrane receptor on myoepithelial cells and causes Ca2+ uptake in these cells, which dere-presses the contractile mechanism. Consequently, ductules and ducts contract and milk is ejected from the gland through the nipple into the infant's mouth. It is not known whether any activities can be ascribed to NP once they have been dissociated from the hormonal complex in the blood.

In the case of terminal uterine contractions at birth, the primary signal for OT release from the posterior pituitary is a marked decline in the level of circulating free progesterone, which was being produced at high levels from the placenta during the latter course of pregnancy. At term, there is a surge of estradiol production with the dramatic decline in free progesterone. Estradiol stimulates the uterine myometrium to become more sensitive to OT by inducing the formation of new OT receptors (Figure 4-20). As a result of this increase in OT receptors in the myometrium, small amounts of oxytocin will stimulate uterine contractions at levels of the hormone that would be ineffective with-

FIGURE 4-20 Concentration of OT receptors in the rat myometrium and mammary gland during pregnancy and lactation. Receptor number is expressed as the specific binding of tritiated OT to particulate fractions (femtomoles/milligram of protein). Reproduced from Lincoln, D. W. (1984). The posterior pituitary. In "Reproduction in Mammals; Book III: Hormonal Control of Reproduction" (C. R. Austin and R. V. Short, eds.), 2nd ed., pp. 21-50. Cambridge Univ. Press, London and New York. Reproduced by copyright permission of Cambridge Univ. Press.

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