Estrogen Promotes Microvascularization in the Fetus and Thus Vascular Function and Insulin Sensitivity in Offspring.

We have shown that normal weight offspring born to estrogen-deprived baboons exhibited insulin resistance, although liver and adipose function and insulin receptor and glucose transporter expression were unaltered. The blood microvessels have an important role in insulin action by delivering insulin and glucose to target cells. Although little is known about the regulation of microvessel development during fetal life, estrogen promotes capillary proliferation and vascular function in the adult.

Adipose and Liver Function in Primate Offspring with Insulin Resistance Induced by Estrogen Deprivation in Utero.

Purpose: We recently demonstrated that offspring delivered to baboons deprived of estrogen during the second half of gestation exhibited insulin resistance. Therefore, because skeletal muscle accounts for >80% of insulin dependent glucose disposal, we suggested that estrogen programs factors in fetal skeletal muscle important for insulin sensitivity in offspring. However, liver and adipose are also sites of insulin action and adipose insulin resistance can increase serum free fatty acid (FFA) levels and thereby reduce skeletal muscle insulin sensitivity.

Insulin resistance elicited in postpubertal primate offspring deprived of estrogen in utero.

We recently demonstrated that offspring delivered to baboons deprived of estrogen during the second half of gestation exhibited insulin resistance prior to onset of puberty. Because gonadal hormones have a profound effect on insulin action and secretion in adults, we determined whether insulin resistance is retained after initiation of gonadal secretion of testosterone and estradiol. Glucose tolerance tests were performed in postpubertal baboon offspring of untreated and letrozole-treated animals (serum estradiol reduced >95 %).

Estrogen deprivation in primate pregnancy leads to insulin resistance in offspring.

This study tested the hypothesis that estrogen programs mechanisms within the primate fetus that promote insulin sensitivity and glucose homeostasis in offspring. Glucose tolerance tests were performed longitudinally in prepubertal offspring of baboons untreated or treated on days 100 to 165/175 of gestation (term is 184 days) with the aromatase inhibitor letrozole, which decreased fetal estradiol levels by 95%. Basal plasma insulin levels were over two-fold greater in offspring delivered to letrozole-treated than untreated animals.

Estrogen Regulation of Fetal Adrenal Cortical Zone-Specific Development in the Nonhuman Primate Impacts Adrenal Production of Androgen and Cortisol and Response to ACTH in Females in Adulthood.

We showed that the volume of the fetal zone of the fetal adrenal gland and serum dehydroepiandrosterone sulfate (DHAS) levels at term were increased in baboons in which estradiol levels were suppressed by treatment with aromatase inhibitor 4,4-[1,2,3-triazol-1yl-methylene] bis-benzonitrite (letrozole). The fetal zone remodels postnatally into the reticular zone and DHAS production, and serum levels decline with age. Therefore, we determined whether the trajectory of reticular zone DHAS secretion and response to ACTH were altered in offspring deprived of estrogen in utero.

Regulation of baboon fetal ovarian development by placental estrogen: onset of puberty is delayed in offspring deprived of estrogen in utero.

Using the baboon as a model for studies of human reproductive biology, we previously showed that placental estrogen regulates fetal ovarian follicle development. In this study, offspring of baboons untreated or treated in utero with the aromatase inhibitor letrozole (estradiol reduced >95%) or letrozole and estradiol were reared to adulthood to determine whether estrogen programming of the fetal ovary impacted puberty and reproduction in adulthood. All offspring exhibited normal growth and blood pressure/chemistries.

The COX-2 inhibitor meloxicam prevents pregnancy when administered as an emergency contraceptive to nonhuman primates.

Objective: Cyclooxygenase-2 (COX-2) inhibitors reduce prostaglandin synthesis and disrupt essential reproductive processes. Ultrasound studies in women demonstrated that oral COX-2 inhibitors can delay or prevent follicle collapse associated with ovulation. The goal of this study was to determine if oral administration of a COX-2 inhibitor can inhibit reproductive function with sufficient efficacy to prevent pregnancy in primates.

Regulation of baboon fetal pituitary prolactin expression by estrogen.

We previously showed that fetal adrenal fetal zone growth was increased and the number of follicles in the fetal ovary reduced in baboons in which estradiol was suppressed by treatment with the aromatase inhibitor letrozole between mid and late gestation periods. Because adrenal/ovarian development was restored in animals treated with letrozole and estradiol, and both tissues express estrogen receptor, we proposed that estrogen regulates fetal adrenal/ovary development via a direct action. However, because prolactin can modulate fetal adrenal and adult pituitary/ovarian function, the current study determined whether estrogen action involved estradiol-regulated changes in fetal prolactin/luteinizing hormone (LH) expression.

Effect of salt on hypertension and oxidative stress in a rat model of diet-induced obesity.

High-salt diet is known to induce or aggravate hypertension in animal models of hypertension and in humans. When Sprague-Dawley rats (n = 60) are fed a moderately high-fat diet (32% kcal fat, 0.8% NaCl) for 10 wk, about one-half develop obesity [obesity prone (OP)] and mild hypertension, whereas the other half [obesity resistant (OR)] maintain body weight equivalent to a low-fat control (C) and are normotensive.