Effects of prolonged exercise on agouti-related protein: a pilot study

Agouti-related protein (AgRP), is a signaling peptide that affects feeding behavior, energy homeostasis, and has also been shown to stimulate the hypothalamic-pituitary-adrenal axis. The purpose of this study was to determine the effects of 90?min of treadmill exercise on circulating AgRP concentrations and the relationship of AgRP responses to cortisol. Seven young males completed a preliminary trial followed by counterbalanced experimental and control trials 4-5?weeks apart. The experimental trial began 2.5?h after consumption of a standard nutrient beverage and consisted of treadmill exercise at 60?% of previously determined VO(2max) for 90?min. Blood samples were collected before (-30 and 0?min), during (18, 36, 54, 72, and 90?min), and following exercise (20, 40, and 60?min). Blood samples were collected in a resting, control trial at the same time points as the experimental trial. Plasma lactate was significantly higher in the exercise than the control trial. Although AgRP increased from 18?min of exercise to peak at 90?min, these increases were not significantly different than values in the control trial. Cortisol responses during the exercise trial were significantly higher than the control trial. AgRP concentrations during early exercise were positively correlated with cortisol levels later in recovery. The obtained data suggest that AgRP concentrations during prolonged steady-state exercise are associated with subsequent cortisol increases, but further study is required to determine whether there is a causal effect.     

Effect of normoglycemia before conception on early pregnancy hormone profiles

Insulin-dependent diabetic women have been shown to have subnormal hormone levels in the first trimester of pregnancy. To determine whether these abnormalities were the result of poor diabetes control, testosterone, androstenedione, human chorionic gonadotropin (HCG), and prolactin were studied longitudinally in diabetic women made normoglycemic before conception (N = 11) and normal (N = 6) control subjects beginning at the fifth week of gestation. HCG levels rose normally in all 11 diabetic and six control subjects and then declined as expected, with peak levels between 8 and 12 wk of gestation. Prolactin levels similarly rose significantly (P less than 0.00001) during the period studied. Plasma androstenedione did not increase during the course of this study, but testosterone levels increased significantly (P = 0.0001). Androgen levels were consistently higher in diabetic subjects despite the normoglycemic state, although the differences reached statistical significance at only one point. This study demonstrates that when normoglycemia is achieved before conception, HCG and prolactin are normal at 5 wk after the last menstrual period. The possibility that androgen levels may be higher in insulin-requiring diabetic women, perhaps due to peripheral hyperinsulinemia, should be explored.     

The effect of estrogen antagonism on progesterone production in early pregnancy in the baboon (Papio cynocephalus)

These studies were designed to investigate the role of estrogen on progesterone production in early pregnancy in the baboon, when the contribution of the corpus luteum and placenta has not been established. Oral administration of the estrogen antagonist MER-25 at two dosage levels (15 and 30 mg/kg/day) to the pregnant baboon from days 35 to 55 after conception results in a decline in peripheral plasma levels of progesterone within a few days and persists for at least 20 days after the termination of treatment with no effect on plasma estradiol levels. The same study was done with the use of a different estrogen antagonist, trioxifene mesylate (5 mg/kg/day), and there was no effect on plasma progesterone, although a transient depression in plasma estradiol was evident. These actions may be due to an inherent estrogenicity of trioxifene. In preliminary studies an effect of these estrogen antagonists on placental size and morphology has been observed. Estrogen deprivation in early pregnancy of the baboon results in a depression in plasma progesterone and indicates a placental requirement for estrogen in progesterone product at this stage of pregnancy.     

When is it safe to switch from oral contraceptives to hormonal replacement therapy?

Women may continue to use oral contraceptives (OCs) into their 40's and 50's, but to date no method has been evaluated to ascertain their ovarian status, i.e., whether fertility and estrogen production have diminished sufficiently so they could be safely switched to hormonal replacement therapy.

A group of 12 postmenopausal women who had been, for long periods of time, on a regimen of 3 back-to-back packages (i.e., 63 days on, 7 days off) of low-dose oral contraceptives have been studied. Secondly, a group of 9 perimenopausal women aged 36 to 47 were examined in the same manner. The third group consisted of early reproductive age women (arbitrarily divided into subsets aged 17–25 and 26–35 using low-dose OCs in the customary regimen) as normal controls. Blood samples were obtained on the last day of a pill cycle and at 7 days off the pill. In some menopausal women, blood samples were obtained at both 7 and 14 days off OCs. Serum was assayed by RIA for estradiol, FSH and LH.

As expected in the young reproductive age women, estradiol levels increase at one week off the pill, together with a rebound in FSH and LH to follicular phase levels. In the perimenopausal group, there was a sharp distinction based on age. The women over 40 showed a more marked rise in FSH while those aged 36–40 showed a distinctly lesser response. Estradiol levels were variable, but tended to show some age grouping. Little diagnostic separation was observed for LH. In postmenopausal women, FSH levels were not always elevated at one week post-pill, and even in a second trial with sampling at one and two weeks off the OC, not all postmenopausal women showed a “menopausal” increase in FSH. The more uniform feature was that estradiol levels never increased above basal values.

The study found that serum estradiol levels increase after a week off the pill in controls, but are unchanged at one and two weeks in the menopausal group. FSH levels rebound normally in reproductive age women and usually, but not always, increase substantially in postmenopausal women. After two weeks off OCs, and increased FSH and/or no change in basal estradiol levels is strong evidence that it is now safe (contraceptively speaking) to switch from OCs to standard hormone replacement regimens.     

Pregnancy: Testosterone and androstenedione in premature ovarian failure pregnancies: evidence for an ovarian source of androgens in early pregnancy

Numerous anecdotal reports but few scientific approaches havesuggested an increase in androgens in early pregnancy. In thisstudy we have compared the concentration of serum androgens,testosterone and androstenedione in early pregnancy, startingwithin the cycle of conception. We have taken the opportunityto study women with premature ovarian failure where pregnancydevelops in the virtual absence of ovarian functions. This studydemonstrates that the concentration of testosterone (0.29 ±0.04 ng/ml) and androstenedione (1.770 ± 0.136 ng/ml)in these subjects is as low as, if not lower than, non-pregnantwomen (0.39 ± 0.02 and 2.170 ± 0.025 ng/ml), significantlyincreased in normal pregnancies (1.190 ± 0.118 and 3.920± 0.297 ng/ml; P < 0.05) and even further increasedin human menopausal gonadotrophin-treated cycles (1.990 ±0.230 and 8.19 ± 0.72 ng/ml; P < 0.05). These studiesdemonstrate that the ovary is a contributor to the circulatingconcentrations of testosterone and androstenedione startingwithin the cycle of conception.     

Hyperprolactinemia inhibits development of Leydig cell tumors in aging Fischer rats

In inbred CDF (Fischer 344) male rats autopsied at the age of 18-24 months, testicular tumors were present in 24 of 36 control animals but in none of 28 males rendered hyperprolactinemic by transplantation of anterior pituitaries from adult females under the renal capsules. In another experiment, microscopically detectable Leydig cell adenomas were present in each of 11 control animals at the age of 14.5 months but in none of 11 males in which hyperprolactinemia was induced by treatment with diethylstilbestrol. Development of testicular tumors had initially little effect on basal and hCG-stimulated plasma testosterone and androstenedione levels but eventually led to atrophy of the seminal vesicles. Incubated tumor tissue produced large quantities of progesterone and responded to hCG in vitro by an increase in progesterone but not testosterone secretion. Daily sperm production and epididymal sperm reserves were significantly reduced already during early stages of Leydig cell tumor development. We propose that hyperprolactin prevents development of Leydig cell tumors by suppression of plasma LH levels and suggest that age-related reductions in gametogenic and steroidogenic functions of the testes in Fischer rats are due to development of Leydig cell tumors rather than to aging per se.