No effect of menstrual cycle phase on glucose and glucoregulatory endocrine responses to prolonged exercise.

INTRODUCTION: Prolonged exercise requires increased utilization of blood glucose and adjustment of glucoregulatory hormones. Estrogen can reduce hepatic gluconeogenesis which could affect insulin concentrations. Amylin is co-secreted with insulin and controls influx of glucose into the blood. PURPOSE: To determine the effect of menstrual cycle stage on glucose, leptin, and pancreatic hormone responses to prolonged (90 min) exercise. METHODS: Five healthy, eumenorrheic women (24.6 ± 5.1 years; 67.4 ± 1 kg) were monitored for 3 months to determine menstrual cycle length. Subjects completed a preliminary session to determine exercise workloads and, in a fasted condition, completed two randomized 90-min treadmill exercise trials at 60 % VO2max during the early follicular (EFX) and mid-luteal phase (MLX) of their menstrual cycle. Blood samples were analyzed for glucose, insulin, C-peptide, amylin, glucagon, leptin, and cortisol concentrations at rest (-30 and 0 min), during exercise (18, 36, 54, 72, and 90 min) and after 20 min of recovery. RESULTS: No changes in amylin, leptin, or cortisol occurred for EFX and MLX trials. A significant (p < 0.05) time effect occurred for glucose, insulin, and glucagon with reduced insulin across the exercise trial and increases in glucose and glucagon later in the trial, but there were no differences between the EFX and MLX trials. CONCLUSIONS: Menstrual cycle stage does not affect glucose, insulin, C-peptide, amylin, glucagon, cortisol, and leptin responses to prolonged exercise; however, the exercise reduces insulin and increases glucose and glucagon concentrations. This is the first study to determine acute effects of exercise on amylin and other glucoregulatory hormone responses in women.

Neuroendocrine responses to psychological stress in eumenorrheic and oligomenorrheic women.

Neuroendocrine adaptive responses to psychological stress include activation of the hypothalamic-pituitary-adrenal (HPA) axis and sometimes suppression of the hypothalamic-pituitary-gonadal (HPG) axis. In women who experience chronic stress, these responses are probably responsible for disturbances in the menstrual cycle. In the present experiment, we investigated the effect of an acutely stressful situation on the physiological and neuroendocrine responses in college age women. We hypothesized that females who are experiencing some degree of abnormal menstrual function or women who have less-robust cycles (oligomenorrheic females) would exhibit differences in gonadotropin secretion from eumenorrheic females when exposed to psychological stressors. Fifteen women completed this study: eumenorrheic (n = 5) and oligomenorrheic women (n = 5) who experienced a series of psychological stressors, and eumenorrheic controls (n = 5). Blood samples were taken at 10 min intervals for 8 h (09:00-17:00) in each woman during the mid-follicular phase of the menstrual cycle. The psychological stressors were administered for 1 h beginning at 13:00 h. Luteinizing hormone (LH), growth hormone (GH) and cortisol were measured in each sample to assess the effect of stress on secretion of these hormones. Deconvolution analysis was used to analyze pulsatile hormone secretion and the approximate entropy (ApEn) statistic analyzed the regularity of release of each hormone. Although, there were significant changes in heart rate (HR), skin resistance (SR) and cortisol levels in the stressed women during the psychological stressor compared to resting baseline values but not in the controls, there was no difference in either LH or GH secretion between women who experienced stress and those who did not. Furthermore, there were no differences in the LH or GH secretion patterns in the oligomenorrheic and eumenorrheic women exposed to the psychological stressor.

Hypoglycemia-induced suppression of luteinizing hormone (LH) secretion in intact female rhesus macaques: role of vasopressin and endogenous opioids.

The first objective of this study was to determine whether insulin-induced hypoglycemia (IIH) inhibits LH secretion in unrestrained female macaques during the follicular phase of the menstrual cycle. There was a consistent inhibitory effect of hypoglycemia on LH secretion within 3 h in these females. This inhibition was likely an indirect effect since low glucose levels did not inhibit GnRH secretion from GT1-1 neurones in vitro. We next investigated whether administration of a vasopressin antagonist (AVPa) either alone, or with naloxone could reverse the IIH-induced inhibition of LH release. Females were studied in the follicular phase during 10 h periods with blood samples collected every 10 min. Experimental groups were IIH (n=6), IIH+AVPa (n=5) and IIH+AVPa+naloxone (n=4). The first 5 h of each study served as a control and hypoglycemia was then induced with insulin. The AVPa was given as a bolus (180 microg) just before the insulin and was followed by a continuous infusion (180 microg/h) for 5 h. Naloxone (5 mg/kg) was given with the AVPa and followed by a continuous infusion (5 mg/kg/h) for 5 h. In the IIH group, LH reached its lowest value 3-4 h after insulin. Neither AVPa nor AVPa+naloxone infusion reversed the inhibitory action of hypoglycemia on LH release. These data suggest that if there are inhibitory actions of vasopressin and endogenous opioids on GnRH release induced by hypoglycemia, they are not sufficient to explain the suppression of GnRH/LH release in intact female primates.

Leptin and reproductive function in males.

Leptin is a circulating protein produced by adipocytes that has been implicated in control of body weight through appetite regulation and control of reproduction, most likely through an effect on the central nervous system. From studies in mice, it is clear that the genetic background of the animal on which the mutation in the leptin gene is placed can influence how that mutation is expressed. Although the effects of leptin have been more thoroughly documented in nonprimate species than in primates, a few human families with genetic mutations of the gene for leptin or the leptin receptor show obesity and impaired fertility. There is conflicting evidence regarding the effects of leptin in male primates, but it appears that the metabolic and reproductive effects of low leptin levels caused by reduced energy intake in adult animals can be more readily alleviated by administration of energy substrates than by administration of leptin.

Glucose relays information regarding nutritional status to the neural circuits that control the somatotropic, corticotropic, and gonadotropic axes in adult male rhesus macaques.

In male mammals, the neuroendocrine responses to fasting include increased GH and cortisol secretion and suppressed LH and T levels. Because blood glucose levels fall during fasting, we hypothesized that this modest, but consistent, change in blood glucose was a metabolic signal for the neuroendocrine adjustments of reproductive and metabolic hormones. Glucose (D-dextrose, 480 kcal/d) was infused into fasted (48 h) adult male rhesus macaques; and LH, cortisol, and GH were measured in plasma from samples collected at 15-min intervals for the last 15 h of the fast. We analyzed hormone secretion by deconvolution analysis, and the orderliness of release patterns by the approximate entropy statistic. Circulating blood glucose was 76 +/- 7 mg/dl in the fed control group, significantly higher (P < 0.01) than the level of 56 +/- 3 mg/dl in the fasted group. The increase in GH pulsatility and the 2-fold elevation in cortisol levels observed in the fasted male macaques were prevented by parenteral glucose delivery. The suppression of LH in fasted animals was not relieved by glucose infusions but seemed to be partially prevented in three of the animals. These findings are consistent with the hypothesis that glucose serves as a signal of nutritional status controlling adaptive neuroendocrine responses to fasting in the primate.

Floor Space Needs for Laboratory Mice: C56BL/6 Males in Solid-bottom Cages with Bedding.

Measures of performance, mortality, adrenal weights, plasma glucocorticoid concentration, and selected immune measures were collected in an attempt to define space needs of laboratory mice. Six replications of 3 C57BL/6 male mice per cage were examined while housed on bedding at 5, 10, 15, or 20 in(2) (32.2, 64.5, 96.8, or 129 cm(2)) per mouse. Body weights were not influenced by treatment; however, mice in smaller spaces (5 in(2) per mouse) consumed or wasted more feed and water than mice given greater space allowances. Mice given the least amount of space (5 in(2) per mouse) had greater lymphocyte proliferation in response to the T-cell mitogen PHA than mice given more space. Mice provided 10 in(2) per mouse had greater natural killer cytotoxicity than mice given greater or less space. Mouse mortality was greater as more space was provided. In contrast, adrenal weights and plasma glucocorticoid concentrations were progressively greater with lower space allowances. The National Research Council 1996 recommendation of 15 in(2) per mouse, for this strain and sex of mice, would result in greater mortality and reduced activity of some immune measures. Socially housed male C57BL/6 mice will benefit from less space than recommended by the National Research Council in 1996.