Background: Epidemiologic, animal, and human data suggest that progestins are potent endometrial cancer preventive agents. In the ovarian surface epithelium, progestins have been hypothesized to confer a cancer preventive effect via apoptosis and modulation of transforming growth factor-B (TGF-B). Given that the ovarian epithelium and endometrium share a common embryologic origin and similar reproductive and hormonal risk factors for malignancy, we tested the hypothesis that progestins confer biological effects in the endometrium similar to those in the ovary. Methods: Postmenopausal female macaques (n = 78) were randomized into four groups to receive a diet for 36 months containing no hormone versus conjugated equine estrogen (CEE), medroxyprogesterone acetate (MPA), or CEE + MPA. The endometrium was then examined immunohistochemically for treatmentspecific changes using antibodies to activated caspase-3

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SUMMARY Participation of vasopressin arid the renin-anglotensin system in the maintenance, of systemic arterial pressure was evaluated in unanesthetized adrenalectomized rats. Adrenalectomized and sham-operated rats with implanted arterial and venous catheters were given 1% sodium chloride and 2.5% glucose as drinking fluid for 72 hours following adrenalectomy. Serum and urine samples were obtained for measurement of electrolyte and solute concentration. The pattern of serum electrolytes, serum osmolality, and renal excretion of electrolytes, solute, and water observed in the adrenalectomized rats was entirely consistent with previous observations in this model. Mean arterial pressure of unanesthetized unrestrained adrenalectomized rats was significantly lower than controls. In adrenalectomized rats, dPMeTyrAVP reduced mean arterial pressure 9 ± 1 mm Hg, p < 0.001; captopril then caused an additional reduction of 17 ± 2 mm Hg, p < 0.01. Neither antagonist altered arterial pressure in the control group. Our results indicate that vasopressin and the renin-angiotensin system play a compensatory pressor role in adrenal insufficiency, preventing a larger decrease of arterial pressure in this model of chronic hypotension. son's disease) and adrenalectomized animals have a tendency to arterial hypotension. Activation of the renin-angiotensin pressor. system is a well-documented compensatory mechanism in both clinical and experimental adrenal insufficiency.1 -2 Circulating levels of vasopressin are elevated in clinical adrenal insufficiency 3 and in experimental forms of glucocorticoid and/or mineralocorticoid deficiency.4 " 6 A compensatory role for the pressor effect of vasopressin has been described in experimentally induced hypovolemic states such as dehydration in the rat 7 and hemorrhage in the dog 8 ' 9 by means of the use of specific antagonists of this hormone. Recently, it has been established that the increased circulating levels of vasopressin in adrenal insufficiency in dogs are high enough to exert a pressor effect. 6 We evaluated the contributions of both vasopressin and the renin-angiotensin system to maintenance of systemic arterial pres- sure in rats with experimental adrenal insufficiency by use of specific antagonists. Evidence is presented that both peptide systems participate in controlling arterial pressure in this model. MethodsFemale Sprague Dawley rats with an approximate weight of 250 g were placed in individual metabolic cages for a 3-day period of habituation after whicl v they underwent either adrenalectomy or sham adrerialectomy through a lumbar incision. Surgery was carried out during anesthesia with ketamine (100 mg/kg ip). At this time a Tygon (Norton) catheter was inserted into the left carotid artery and advanced to the thoracic descending aorta. Two catheters were inserted in the left jugular vein and advanced to the superior vena cava, just proximal to the right atrium., All three catheters were exteriorized at the back of the heck, filled with heparin (100 U/ml), and capped with pl...

The effect of vasopressin infusion on the pressor dose responses to angiotensin II and norepinephrine was studied in pentobarbital-anesthetized and unanesthetized nephrectomized rats. Pressor vasopressin (2-15 ng X kg-1 X min-1) given to anesthetized rats decreased sensitivity to angiotensin II in a dose-dependent manner (r = 0.88), an effect completely reversible by dPMeTyrAVP, a vasopressin vascular antagonist. Subpressor vasopressin (0.5-1 ng X kg-1 X min-1) given to unanesthetized rats diminished sensitivity to angiotensin II in the presence or absence of pentolinium (10 mg/kg). Shifts in dose-response curves to angiotensin II were always parallel. In contrast, dose responses to norepinephrine were not modified by vasopressin in pentolinium-treated rats and showed a small nonparallel rightward shift in animals without pentolinium. In animals without pentolinium, the baroreflex-mediated reduction in heart rate elicited by angiotensin II was not altered by vasopressin infusion. Our data suggest that vasopressin reduces angiotensin II pressor action by diminishing pressor sensitivity to the peptide. They indicate that the effect may be specific, mediated through the vascular receptor for vasopressin and independent of actions of this hormone on the autonomic nervous system.