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Ganong's Review of Medical Physiology, 23rd Edition

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VASOPRESSIN & OXYTOCIN<br />

IN OTHER LOCATIONS<br />

Vasopressin-secreting neurons are found in the suprachiasmatic<br />

nuclei, and vasopressin and oxytocin are also found in<br />

the endings <strong>of</strong> neurons that project from the paraventricular<br />

nuclei to the brain stem and spinal cord. These neurons appear<br />

to be involved in cardiovascular control. In addition, vasopressin<br />

and oxytocin are synthesized in the gonads and the<br />

adrenal cortex, and oxytocin is present in the thymus. The<br />

functions <strong>of</strong> the peptides in these organs are unsettled.<br />

Vasopressin Receptors<br />

There are at least three kinds <strong>of</strong> vasopressin receptors: V 1A,<br />

V 1B, and V 2. All are G protein-coupled. The V 1A and V 1B receptors<br />

act through phosphatidylinositol hydrolysis to increase<br />

the intracellular Ca 2+ concentration. The V 2 receptors<br />

act through G s to increase cAMP levels.<br />

Effects <strong>of</strong> Vasopressin<br />

Because one <strong>of</strong> its principal physiologic effects is the retention<br />

<strong>of</strong> water by the kidney, vasopressin is <strong>of</strong>ten called the antidiuretic<br />

hormone (ADH). It increases the permeability <strong>of</strong> the<br />

collecting ducts <strong>of</strong> the kidney so that water enters the hypertonic<br />

interstitium <strong>of</strong> the renal pyramids (see Chapter 38). The<br />

urine becomes concentrated and its volume decreases. The<br />

overall effect is therefore retention <strong>of</strong> water in excess <strong>of</strong> solute;<br />

consequently, the effective osmotic pressure <strong>of</strong> the body fluids<br />

is decreased. In the absence <strong>of</strong> vasopressin, the urine is hypotonic<br />

to plasma, urine volume is increased, and there is a net<br />

water loss. Consequently, the osmolality <strong>of</strong> the body fluid rises.<br />

Effects <strong>of</strong> Oxytocin<br />

In humans, oxytocin acts primarily on the breasts and uterus,<br />

though it appears to be involved in luteolysis as well (see<br />

Chapter 25). A G protein-coupled serpentine oxytocin receptor<br />

has been identified in human myometrium, and a similar<br />

or identical receptor is found in mammary tissue and the ovary.<br />

It triggers increases in intracellular Ca 2+ levels.<br />

The Milk Ejection Reflex<br />

Oxytocin causes contraction <strong>of</strong> the myoepithelial cells, smoothmuscle-like<br />

cells that line the ducts <strong>of</strong> the breast. This squeezes<br />

the milk out <strong>of</strong> the alveoli <strong>of</strong> the lactating breast into the large<br />

ducts (sinuses) and thence out <strong>of</strong> the nipple (milk ejection).<br />

Many hormones acting in concert are responsible for breast<br />

growth and the secretion <strong>of</strong> milk into the ducts (see Chapter 25),<br />

but milk ejection in most species requires oxytocin.<br />

Milk ejection is normally initiated by a neuroendocrine<br />

reflex. The receptors involved are the touch receptors, which are<br />

plentiful in the breast—especially around the nipple. Impulses<br />

generated in these receptors are relayed from the somatic touch<br />

CHAPTER 18 Hypothalamic Regulation <strong>of</strong> Hormonal Functions 279<br />

pathways to the supraoptic and paraventricular nuclei. Discharge<br />

<strong>of</strong> the oxytocin-containing neurons causes secretion <strong>of</strong><br />

oxytocin from the posterior pituitary (Figure 18–8). The infant<br />

suckling at the breast stimulates the touch receptors, the nuclei<br />

are stimulated, oxytocin is released, and the milk is expressed<br />

into the sinuses, ready to flow into the mouth <strong>of</strong> the waiting<br />

infant. In lactating women, genital stimulation and emotional<br />

stimuli also produce oxytocin secretion, sometimes causing<br />

milk to spurt from the breasts.<br />

Other Actions <strong>of</strong> Oxytocin<br />

Oxytocin causes contraction <strong>of</strong> the smooth muscle <strong>of</strong> the uterus.<br />

The sensitivity <strong>of</strong> the uterine musculature to oxytocin is<br />

enhanced by estrogen and inhibited by progesterone. The inhibitory<br />

effect <strong>of</strong> progesterone is due to a direct action <strong>of</strong> the<br />

steroid on uterine oxytocin receptors. In late pregnancy, the<br />

uterus becomes very sensitive to oxytocin coincident with a<br />

marked increase in the number <strong>of</strong> oxytocin receptors and oxytocin<br />

receptor mRNA (see Chapter 25). Oxytocin secretion is<br />

increased during labor. After dilation <strong>of</strong> the cervix, descent <strong>of</strong><br />

the fetus down the birth canal initiates impulses in the afferent<br />

nerves that are relayed to the supraoptic and paraventricular<br />

nuclei, causing secretion <strong>of</strong> sufficient oxytocin to enhance labor<br />

(Figure 25-32). The amount <strong>of</strong> oxytocin in plasma is normal<br />

at the onset <strong>of</strong> labor. It is possible that the marked increase<br />

in oxytocin receptors at this time causes normal oxytocin levels<br />

to initiate contractions, setting up a positive feedback.<br />

However, the amount <strong>of</strong> oxytocin in the uterus is also increased,<br />

and locally produced oxytocin may also play a role.<br />

Oxytocin may also act on the nonpregnant uterus to facilitate<br />

sperm transport. The passage <strong>of</strong> sperm up the female genital<br />

tract to the uterine tubes, where fertilization normally takes<br />

place, depends not only on the motile powers <strong>of</strong> the sperm but<br />

also, at least in some species, on uterine contractions. The genital<br />

stimulation involved in coitus releases oxytocin, but it has<br />

not been proved that it is oxytocin which initiates the rather<br />

specialized uterine contractions that transport the sperm. The<br />

secretion <strong>of</strong> oxytocin is increased by stressful stimuli and, like<br />

that <strong>of</strong> vasopressin, is inhibited by alcohol.<br />

Circulating oxytocin increases at the time <strong>of</strong> ejaculation in<br />

males, and it is possible that this increase causes increased<br />

contraction <strong>of</strong> the smooth muscle <strong>of</strong> the vas deferens, propelling<br />

sperm toward the urethra.<br />

CONTROL OF ANTERIOR<br />

PITUITARY SECRETION<br />

ANTERIOR PITUITARY HORMONES<br />

The anterior pituitary secretes six hormones: adrenocorticotropic<br />

hormone (corticotropin, ACTH), thyroid-stimulating<br />

hormone (thyrotropin, TSH), growth hormone, folliclestimulating<br />

hormone (FSH), luteinizing hormone (LH),

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