Characterization of a hepatic protein in nonhuman primates that binds mibolerone but not dihydrotestosterone or methyltrienolone.

During our studies of the hepatic androgen receptor in cynomolgus monkeys, tritiated mibolerone +/- a 200-fold excess of unlabeled mibolerone has been used to determine specific binding in cytosol. During time-course studies, high-capacity, unsaturable binding of [3H]mibolerone was noted after short-term incubations (4 h, 4 degrees C). When hepatic cytosol from male monkeys was incubated for 18 h at 4 degrees C, the high-capacity binding disappeared; saturable, high-affinity binding with characteristics consistent with the androgen receptor then could be identified.

Noradrenergic vasorelaxation of porcine coronary arteries is enhanced by direct, acute exposure to 17 beta-estradiol.

1. We tested whether responses of isolated coronary arteries to adrenergic agents are altered by overnight (18-22 hr) or acute exposure to physiological levels of 17 beta-estradiol. 2.

17 beta-estradiol treatment increases the levels of estrogen receptor and its mRNA in male rat liver.

This study examined estrogen receptor dynamics in the livers of male obese rats (SHHF/Mcc-cp) treated for two weeks with a continuous, low dose of 17 beta-estradiol compared with untreated controls. An increased binding capacity for tritiated 17 beta-estradiol in the cytosol, consistent with binding to the estrogen receptor, was demonstrated in treated males relative to control males (P < 0.01).

Estrogen pretreatment directly potentiates endothelium-dependent vasorelaxation of porcine coronary arteries.

We tested whether vasorelaxation of coronary arteries is altered after overnight (18-22 h) exposure to physiological levels of 17 beta-estradiol. Ring segments of left circumflex coronary artery from six female and six castrated male pigs were incubated in vials of sterile Dulbecco's modified Eagle's medium with 1 nM 17 beta-estradiol, 1 nM 17 beta-estradiol + 10 nM tamoxifen, 1 nM 17 alpha-estradiol, or estrogen vehicle (ethanol) under normoxic conditions in an O2-CO2 incubator at 37 degrees C for 18-22 h. Coronary rings, with and without endothelium, were then suspended in vessel baths for measurement of isometric force.

Effect of obesity and fertility status on sex steroid levels in men.

Endocrine studies were performed on fertile and infertile obese men and compared with fertile and infertile nonobese men in order to determine the independent and codependent effects of obesity and fertility status on the male hypothalamic-pituitary gonadal axis. The obese infertile group exhibited significant endocrinologic changes as compared with fertile nonobese control group which was not observed in any of the other three groups. Serum testosterone was significantly lower.

Inhibition of coronary artery atherosclerosis by 17-beta estradiol in ovariectomized monkeys. Lack of an effect of added progesterone.

Although controversy continues, the preponderance of evidence indicates that estrogen replacement therapy favorably influences the risk of coronary heart disease in postmenopausal women. It remains uncertain how this effect is mediated and whether the cyclic addition of a progestin may influence adversely an estrogen-related cardioprotective effect. We investigated the influence of sex hormone replacement therapy on diet-induced coronary artery atherosclerosis in estrogen-deficient (ovariectomized) adult female cynomolgus monkeys.

Progesterone and estradiol concentrations in nonpregnant and pregnant human myometrium. Effect of progesterone and estradiol on cyclic adenosine monophosphate-phosphodiesterase activity.

We measured the concentration of progesterone and estradiol and calculated the progesterone:estradiol ratio in nonpregnant and pregnant human myometrium. Progesterone, estradiol and the progesterone:estradiol ratio were higher in pregnant than in nonpregnant myometrium. There was no difference in the concentration in the presence of labor.

Hormonal determinants of apolipoprotein B,E receptor expression in human liver. Positive association of receptor expression with plasma estrone concentration in middle-aged/elderly women.

The relationships of the expression of hepatic low-density lipoprotein (LDL) receptors (apo B,E receptors) to several plasma hormone concentrations were examined in 15 fasted women aged 37-75 years (mean, 57 years), who were undergoing laparotomy for non-neoplastic disease. No subject had clinical or biochemical evidence of familial hypercholesterolemia, renal disease, hepatic disease, or endocrine disease. Hepatic apo B,E receptor expression was quantified in vitro as the EDTA-suppressible binding of 125I-labeled human LDL (15 micrograms protein/ml) by liver homogenate at 37 degrees C; values were 23-75 ng LDL protein/mg cell protein (mean, 47 ng/mg).

Differential effects of oral estrone versus 17 beta-estradiol on lipoproteins in postmenopausal women.

Toward the definition of optimal postmenopausal estrogen replacement we compared the effects of three graduated doses of two oral estrogens, estrone sulfate and 17 beta-estradiol, on the lipid profiles of two groups of six postmenopausal women. Because of metabolic interconversions equivalent serum concentrations of estrone and estradiol were produced with these regimens. However, differential effects were noted in lipoproteins.

Oral contraceptive administration, interfemale relationships, and sexual behavior in Macaca fascicularis.

The effects of oral contraceptive administration on the social relationships of adult female cynomolgus monkeys (Macaca fascicularis) were examined. Ten females were administered ethinyl estradiol/ethynodiol diacetate (Demulen), 10 were administered ethinyl estradiol/norgestrel (Ovral), and 10 served as a control group. The monkeys lived in social groups of 5 females each, and patterns of social interaction and social status were recorded.

Oral contraceptives and coronary artery atherosclerosis of cynomolgus monkeys.

Studies of both human and nonhuman primates show an inverse relationship between high-density lipoprotein (HDL) cholesterol concentrations and coronary artery atherosclerosis. For this reason, there has been concern that the HDL cholesterol-lowering effect of oral contraceptives might exacerbate coronary artery atherosclerosis. We studied three groups of adult female cynomolgus macaques fed a moderately atherogenic diet: a control group, a group given ethinyl estradiol and norgestrel, and another group given ethinyl estradiol and ethynodiol diacetate.

Cardiovascular and testosterone responses to contested dominance in women.

Examined cardiovascular and testosterone responses of dominant and submissive women to an acute stressor involving contested dominance. Twenty (10 dominant, 10 submissive) university students rated their dominance to a predefined reference group, participated in a task that involved debating with a trained technician, and were continuously provided with bogus feedback throughout the task concerning biochemical substances in their blood that purportedly covaried with dominance. Covariance analyses revealed that dominant women were much more reactive to the stressor in several cardiovascular parameters than those classified as submissive.

Treatment of oophorectomized guinea pigs with intrauterine 17 beta-estradiol pellets may modulate myometrial beta-adrenergic receptor binding properties.

Intrauterine 17 beta-estradiol pellets can induce an up-regulation of guinea pig myometrial beta-adrenergic receptor density and l-isoproterenol-dependent adenylate cyclase activity. Does 17 beta-estradiol influence the ability of beta-adrenergic receptors to form a "high affinity" state with l-isoproterenol, which is a necessary step for adenylate cyclase activation? Nonpregnant, oophorectomized guinea pigs received intrauterine pellets of either placebo, 17 beta-estradiol, progesterone, or 17 beta-estradiol plus progesterone for 1 week. 17 beta-Estradiol resulted in pharmacologic, whereas progesterone resulted in physiologic plasma 17 beta-estradiol and progesterone concentrations, respectively.

Up-regulation of guinea pig myometrial adenylate cyclase activity by intrauterine estradiol and progesterone pellets.

The effects of intrauterine implantation of 17 beta-estradiol and progesterone on basal and stimulated adenylate cyclase activity in guinea pig myometria were studied in nonpregnant, previously oophorectomized guinea pigs receiving intrauterine implants of either estradiol, progesterone, a combination of the two hormones, or placebo for 7 days. Guanine nucleotides resulted in a significant increase in basal enzymatic activity. The extent of enzymatic stimulation in estradiol-treated animals was significantly higher than that observed in either controls, animals receiving progesterone, or a combination of estradiol and progesterone.

From menarche to menopause: coronary artery atherosclerosis and protection in cynomolgus monkeys.

The effects on atherogenesis of stress, pregnancy, and oral contraceptive therapy were studied in a nonhuman primate model. The stress of social subordination was associated with ovarian dysfunction, unfavorable lipoprotein changes, and increased coronary artery atherosclerosis compared with nonstressed (socially dominant) or normal monkeys. Although pregnant animals exhibited lower high-density lipoprotein cholesterol concentrations, they had only one half as much diet-induced coronary artery atherosclerosis as their nonpregnant counterparts.

Up-regulation of guinea pig myometrial beta-adrenergic receptors by intrauterine estradiol and progesterone pellets.

The effect of intrauterine implantation of 17 beta-estradiol and progesterone on the concentration and affinity of myometrial beta-adrenergic receptor were studied in nonpregnant, previously oophorectomized guinea pigs receiving intrauterine implants of either 17 beta-estradiol, progesterone, a combination of the two hormones, or placebo for 7 days. Myometrial beta-adrenergic receptors were characterized by use of (-)-iodine 125-cyanopindolol as the specific beta-adrenergic receptor ligand. On comparison with the control group, administration of 17 beta-estradiol or progesterone resulted in a severalfold increase in the concentration (Bmax) of myometrial beta-adrenergic receptor and a lesser but significant increase in the dissociation constant, KD.

Acute stress reactivity from contested dominance in dominant and submissive males.

We examined the cardiovascular and testosterone responses of dominant and submissive males to an interpersonal challenge of dominance status. Twenty college-aged students rated their dominance to predefined reference groups and engaged in a debate against a trained technician. Throughout the task, they were continuously given false feedback regarding biochemical substances in the plasma that purportedly covaried with dominance.

Up-regulation of guinea pig myometrial beta-adrenoreceptors by systemic estradiol and progesterone.

The effects of systemic administration of 17 beta-estradiol (E2) and progesterone (P) on the concentration and affinity of myometrial beta-adrenoreceptors were studied in non-pregnant, previously oophorectomized guinea pigs receiving a continuous infusion of E2, P, a combination of the two hormones, or placebo for 7 days. Myometrial beta-adrenoreceptors were characterized by using (-)-[125I-cyanopindolol as the specific beta-adrenoreceptor ligand. Compared to that in the control group, E2 administration resulted in a 7-fold increase in the density of myometrial beta-adrenoreceptors.

Anabolic steroids and aggressive behavior in cynomolgus monkeys.

An animal model was employed to examine the effect of testosterone on aggressive behavior patterns. Ten cynomolgus monkeys were assigned to either an experimental or a control group and given biweekly injections; the experimental group received testosterone propionate, and the controls a sham solution. Prior to and upon the completion of an 8-week treatment period, behavioral observations were conducted.

Pregnancy-associated inhibition of coronary artery atherosclerosis in monkeys. Evidence of a relationship with endogenous estrogen.

We investigated the influence of repeated pregnancy on diet-induced atherosclerosis in cynomolgus monkeys and sought to determine if circulating endogenous reproductive steroid levels were associated with the extent of coronary artery atherosclerosis. At necropsy, females which were pregnant one or more times were found to have coronary artery atherosclerosis which was one-fourth as extensive as that of intact females which had not been pregnant. Extent of coronary artery atherosclerosis correlated positively with mean total plasma cholesterol (Rho = 0.

Pituitary response to intravenous hypothalamic releasing peptides in cynomolgus monkeys treated with contraceptive steroids.

The secretory response of the pituitary to an iv bolus dose of hypothalamic releasing peptides (HRP) was evaluated in male and cycling (CYC) or contraceptive-treated female cynomolgus monkeys. Parenteral delivery of levonorgestrel and 17 beta-estradiol by intravaginal ring (CVR) was compared with oral administration (OC) of norgestrel and ethinyl estradiol in the diet. LH secretion was suppressed in the CVR group compared to that in other groups, and the response in males was greater than that in either CYC or OC females (P less than 0.