Previous work has indicated that acute and repeated stress can alter thyroid hormone secretion. Corticosterone, the end product of hypothalamic-pituitary-adrenal (HPA) axis activation and strongly regulated by stress, has been suggested to play a role in hypothalamic-pituitary-thyroid (HPT) axis regulation. In the current study, we sought to further characterize HPT axis activity after repeated exposure to inescapable foot-shock stress (FS), and to examine changes in proposed regulators of the HPT axis, including plasma corticosterone and hypothalamic arcuate nucleus agouti-related protein (AGRP) mRNA levels. Adult male Sprague-Dawley rats were subjected to one daily session of inescapable FS for 14 days. Plasma corticosterone levels were determined during and after the stress on days 1 and 14. Animals were killed on day 15, and trunk blood and brains were collected for measurement of hormone and mRNA levels. Repeated exposure to FS led to a significant decrease in serum levels of 3,5,3′-triiodothyronine (T₃) and 3,5,3′,5′-tetraiodothyronine (T₄). Stress-induced plasma corticosterone levels were not altered by repeated exposure to the stress. Despite the decrease in peripheral hormone levels, thyrotropin-releasing hormone (TRH) mRNA levels within the paraventricular nucleus of the hypothalamus were not altered by the stress paradigm. Arcuate nucleus AGRP mRNA levels were significantly increased in the animals exposed to repeated FS. Additionally, we noted significant correlations between stress-induced plasma corticosterone levels and components of the HPT axis, including TRH mRNA levels and free T₄ levels. Additionally, there was a significant correlation between AGRP mRNA levels and total T₃ levels. Changes in body weight were also correlated with peripheral corticosterone and TRH mRNA levels. These results suggest that repeated exposure to mild-electric foot-shock causes a decrease in peripheral thyroid hormone levels, and that components of the HPA axis and hypothalamic AGRP may be involved in stress regulation of the HPT.

No abstract

Cross-sectional and short-term prospective studies in humans support the concept that low energy availability, and not other factors associated with exercise, causes the development of exercise-induced reproductive dysfunction. To rigorously test this hypothesis, we performed a longitudinal study, examining the role of low energy availability on both the development and the reversal of exercise-induced amenorrhea, using a monkey model (Macaca fascicularis). Eight adult female monkeys developed amenorrhea (defined as absence of menses for at least 100 d, with low and unchanging concentrations of LH, FSH, E2, and P4) after gradually increasing their daily exercise to 12.3 +/- 0.9 km/d of running over a 7- to 24-month period. Food intake remained constant during exercise training. To test whether amenorrhea is caused by low energy availability, four of the eight amenorrheic monkeys were provided with supplemental calories (138-181% of calorie intake during amenorrhea) while they maintained their daily training. All four monkeys exhibited increased reproductive hormone levels and reestablished ovulatory cycles, with recovery times for circulating gonadotropin levels ranging from 12-57 d from the initiation of supplemental feeding. The rapidity of recovery within the reproductive axis in a given monkey was directly related to the amount of energy that was consumed during the period of supplemental feeding (r = -0.97; P < 0.05). Repeated measurements of plasma T3 concentrations, a marker of cellular energy availability, revealed a tight correlation between the changes in reproductive function and T3 levels, such that T3 significantly decreased (27%) with the induction and significantly increased (18%) with the reversal of amenorrhea (P < 0.05). These data provide strong evidence that low energy availability plays a causal role in the development of exercise-induced amenorrhea.

This study was designed to test the hypothesis that endogenous opioid peptides (EOP) mediate the negative feedback action of estradiol on GnRH pulse size in breeding season ewes. If this hypothesis is correct, one would predict that an EOP antagonist should increase GnRH pulse size in estradiol-treated ovariectomized (OVX+E), but not in OVX, ewes. We, therefore, examined the effects of naloxone on GnRH pulse profiles in the hypophyseal portal blood of OVX and OVX+E ewes (n = 6/group). Samples were collected every 10 min for 6 h before, 6 h during, and 4 h after naloxone infusion. Estradiol treatment decreased GnRH pulse size and increased GnRH pulse frequency. Naloxone treatment had no effect on GnRH pulse frequency, but significantly increased GnRH pulse size. However, this stimulatory action of naloxone on GnRH pulse size was evident in both OVX and OVX+E ewes. These results are thus not consistent with the hypothesis that EOP mediate the negative feedback action of estradiol. Interestingly, naloxone not only increased GnRH pulse amplitude, but also prolonged the duration of GnRH release during a pulse. To obtain a more precise characterization of the effects of naloxone on the dynamics of GnRH release, pulse profiles in six OVX ewes were examined in hypophyseal portal blood sampled every minute for 4 h before and 4 h during naloxone infusion. Naloxone again increased both the amplitude and duration of GnRH pulses. The increase in GnRH pulse duration was caused by a prolongation of both the plateau and declining phases of the GnRH pulse. In addition to these effects on GnRH release during a pulse, naloxone increased the amount of GnRH collected between pulses in both experiments. The stimulatory effects of naloxone on GnRH release in OVX ewes indicate that the role of EOP in the control of GnRH is not limited to mediating the feedback actions of steroids. In particular, the dramatic effects of naloxone on GnRH pulse shape and interpulse GnRH levels raise the possibility that EOP play an important role in synchronizing the activity of the GnRH neurons involved in episodic GnRH secretion.

No abstract

No abstract

No abstract

No abstract