naloxone and Infertility--Female

The Damaraland mole-rat is a subterranean mammal exhibiting extreme reproductive skew with a single reproductive female in each colony responsible for procreation. Non-reproductive female colony members are physiologically suppressed while in the colony, exhibiting reduced concentrations of plasma luteinizing hormone (LH) and a decreased response of the pituitary, as measured by the release of bioactive LH, to an exogenous dose of gonadotrophin releasing hormone (GnRH). Removal of the reproductive female from the colony results in an elevation of LH and an enhanced response of the pituitary to a GnRH challenge in non-reproductive females comparable to reproductive females, implying control of reproduction in these individuals by the reproductive female. The Damaraland mole-rat is an ideal model for investigating the physiological and behavioral mechanisms that regulate the hypothalamo-pituitary-gonadal axis. In contrast, we know less about the control of reproduction at the level of the hypothalamus. The immunohistochemistry of the GnRH system of both reproductive and non-reproductive female Damaraland mole-rats has revealed no significant differences with respect to morphology, distribution or numbers of immunoreactive GnRH perikarya. We examined whether the endogenous opioid peptide beta-endorphin was responsible for the inhibition of the release of the GnRH from the neurons indirectly by measuring LH concentrations in these non-reproductive females following single, hourly and 8 hourly injections of the opioid antagonist naloxone. The results imply that the endogenous opioid peptide, beta-endorphin, is not responsible for the inhibition of GnRH release from the perikarya in non-reproductive females. Preliminary data examining the circulating levels of cortisol also do not support a role for circulating glucocorticoids. The possible role of kisspeptin is discussed.

Topics: Africa, Southern; Animals; beta-Endorphin; Female; Gonadotropin-Releasing Hormone; Gonads; Hydrocortisone; Hypothalamo-Hypophyseal System; Immunohistochemistry; Infertility, Female; Kisspeptins; Luteinizing Hormone; Mole Rats; Naloxone; Social Environment

Along with 51 amenorrheic patients the pituitary reactional situation was checked by means of an Gn-RH-stimulation test. Simultaneously to all these women the opiate antagonist Naloxone was infused in a further test series. In 7 from 51 women a significant increase of the LH was demonstrated in comparison to the basic values. Comparing the kinetics of the pituitary gland it was evident, that in all cases the gonadotropin emanation was detective respectively missing after the second Gn-RH-bolus, which followed immediately after the first one. The findings seem to proof the thesis that the endorphins mainly influence the gonadotropin reserve capacity. In cases, where it was possible to objectify the influence--the second pool was missing as well.

Topics: Amenorrhea; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Luteinizing Hormone; Naloxone; Pituitary Hormone-Releasing Hormones

Many studies suggest that the hypothalamic opiate system modulates the secretion of LH and prolactin (PRL) by its effects on catecholamine release. We previously provided evidence that the LH response to the opiate receptor antagonist naloxone (NAL) may depend upon spontaneous activity in the hypothalamic noradrenergic system at the time the drug is administered. Thus, when NAL is given to rats which have low turnovers of hypothalamic norepinephrine (NE), only small transient rises in LH occur. This is contrasted to the effects of NAL on the LH responses of animals with high rates of NE turnover where marked amplification of phasic LH release is observed. In the present studies, we examined the effects of NAL on LH and morphine on PRL responses in androgen-sterilized rats (ASR). These animals do not respond to the positive feedback actions of estrogen by having LH surges, and hypothalamic NE turnovers do not increase during the afternoon as they do in normal rats. Female rats were given a single injection of testosterone propionate (50 micrograms s.c.) at 5 days of life and ovariectomized (OVX) at 100 days of age. Seven days later (day 0), estrogen capsules were inserted subcutaneously, and on day 2, their responses to NAL or morphine were examined. Comparable estrogen-treated gonadectomized controls also were studied. In control rats, NAL (10 mg/kg s.c.) markedly amplified the phasic secretion of plasma LH. In contrast, NAL had no effect on the basal afternoon secretion of LH in ASR. To determine if neonatal androgen treatment deleteriously affected opiate-tuberoinfundibular dopamine (TIDA)-serotonergic interactions, a second series of studies was performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Female; Hypothalamus; Infertility, Female; Luteinizing Hormone; Morphine; Naloxone; Norepinephrine; Pituitary Gland, Anterior; Prolactin; Rats; Rats, Inbred Strains; Testosterone