RESUMO
Cysteamine (CSH), a sulfhydryl agent that promotes disulfide-exchange reactions, was studied for its effects on the immunoreactive (IR) levels and synthesis of oxytocin and vasopressin in the hypothalamus. CSH injection (300 mg/kg s.c.) caused a rapid (1 h) suppression of 35S-cysteine incorporation into hypothalamic arginine vasopressin (VP) and oxytocin (OT). The reduction in labeling persisted for about 8 h; label incorporation was normal within 10 h of CSH administration. The drug did not influence 35S-cysteine incorporation into acid-precipitable protein, nor did it influence 35S-cysteine specific activity in the hypothalamus. In addition, 35S-VP and 35S-OT molecules could not be recovered from hypothalami of CSH-treated rats by subjecting samples to denaturing, reducing and then reoxidizing conditions. Despite the reduction in peptide labeling, CSH treatment produced no alterations in the IR VP and OT contents of hypothalamus or posterior pituitary. These results indicate that CSH causes a true suppression of both VP and OT formation in hypothalamus, and suggest that the effect is either too transient to promote a reduction in endogenous stores of either peptide, or that the drug equally inhibits peptide production and removal (i.e., axonal transport, secretion).
Assuntos
Cisteamina/farmacologia , Hipotálamo/metabolismo , Ocitocina/biossíntese , Vasopressinas/biossíntese , Animais , Cromatografia Líquida de Alta Pressão , Cisteína/metabolismo , Hipotálamo/efeitos dos fármacos , Masculino , Ocitocina/imunologia , Neuro-Hipófise/efeitos dos fármacos , Neuro-Hipófise/metabolismo , Radioimunoensaio , Ratos , Ratos Sprague-Dawley , Radioisótopos de Enxofre , Vasopressinas/imunologiaRESUMO
Short periods of fasting have been shown to cause a significant slowing of pulsatile LH secretion in men and male rhesus monkeys, which appears to result from a slowing of GnRH drive to the reproductive axis. To determine whether an increased activity of endogenous opioid peptides causes this slowing of pulsatile LH secretion, the ability of naloxone administration to reverse the fasting-induced suppression of LH secretion was tested. For this study, 6 adult male rhesus monkeys, with indwelling femoral and jugular venous catheters, were maintained on tether/swivel systems. Naloxone was administered to monkeys as a continuous infusion (0.25 mg/kg/h, with an initial loading dose of approximately 1.0 mg) for 8 h (16.00 to 24.00 h) on a day of normal feeding and again on a day of fasting. The LH response to naloxone was determined by collecting blood samples every 15 min from 12.00 to 24.00 h. LH pulse frequency on a day of normal feeding was 4.0 +/- 0.52 pulses/8 h, and naloxone administration on a day of feeding increased LH pulse frequency to 6.8 +/- 0.86 pulses/8 h. On a day of fasting, LH pulse frequency was 1.67 +/- 0.67 pulses/8 h, and naloxone administration on a day of fasting slightly, but not significantly, increased LH pulse frequency to 2.5 +/- 0.51 pulses/8 h. Similar studies were performed with a higher dose of naloxone (0.625 mg/kg/h, with an initial loading dose of approximately 2.0 mg) and again naloxone administration did not reverse the effects of fasting on pulsatile LH secretion. These results suggest that the slowing of pulsatile LH release that occurs with short periods of food restriction does not result from increased secretion of endogenous opioid peptides.
Assuntos
Privação de Alimentos/fisiologia , Hormônio Luteinizante/metabolismo , Naloxona/farmacologia , Animais , Macaca mulatta , Masculino , Radioimunoensaio , Taxa Secretória/efeitos dos fármacosRESUMO
The hypothesis that the timing of puberty is at least in part stimulated by some 'metabolic signal' that tells the central control system of the reproductive axis that the body is becoming large enough, and that there are enough metabolic fuel stores, to support reproductive function has received considerable attention over the past several decades. However, direct experimental support for the hypothesis that mild metabolic changes, such as those that occur slowly during development, are actually capable of modulating reproductive function has been lacking. Our recent studies have shown that very brief periods of fasting in both male rhesus monkeys and men can modify the pulsatile release of LH and testosterone. In monkeys, missing a single meal is associated with a suppression of mean plasma LH, FSH and testosterone concentrations, and with a slowing of the frequency of pulsatile LH secretion. Current studies are aimed at identifying the specific metabolic signals which cause these changes. It is hoped that the results of these studies will eventually help to answer the question of whether normal metabolic changes occurring during development play a role in timing puberty onset.
Assuntos
Metabolismo , Puberdade/fisiologia , Animais , Jejum , Humanos , Hormônio Luteinizante/metabolismo , Macaca mulatta , Masculino , Reprodução/fisiologia , Maturidade Sexual/fisiologia , Testosterona/metabolismoRESUMO
The effect of administration of estradiol (E2) alone or combined with progesterone upon the circadian rhythm of oxytocin concentrations in cerebrospinal fluid (CSF) was examined in adult ovariectomized rhesus monkeys bearing temporary subarachnoid catheters and maintained in a constant photoperiod (lights on 06.00-18.00 h). Animals were subcutaneously implanted with silastic capsules containing 17 beta-E2 for 6 days and progesterone for the last 3 days of E2 administration. Hourly samples of CSF were collected before, during and after gonadal steroid administration and measured for oxytocin by RIA and reverse-phase high-performance liquid chromatography (RP-HPLC). A significant increase in the serum concentration of E2 and the plasma concentration of oxytocin neurophysin, but not the plasma concentration of oxytocin, was found during gonadal steroid administration. Each animal displayed a dirunal pattern of secretion of oxytocin in CSF with peak and trough levels during light and dark hours, respectively. No significant differences were found across experimental conditions in the following CSF oxytocin parameters: mean level of oxytocin in CSF during the light, dark, or light and dark hours combined; the daily phase or amplitude of the CSF oxytocin rhythm; the peak or nadir concentration of oxytocin in CSF; or the total amount of oxytocin secreted into the CSF as expressed as the area under the curve (multivariate repeated measures ANOVA). The CSF oxytocin parameters in the animals that were restudied using empty silastic implants were not significantly different across time (multivariate repeated measures ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)