naloxone and Anovulation

This experiment was conducted to investigate the effect of naloxone (NAL), an opioid receptor antagonist, on pituitary LH secretion in anovulatory Holstein cows during the early postpartum period when cows were expected to be in negative net energy balance. Twenty-three cows (11 primiparous) received either saline (n = 12) or 1 mg/kg BW NAL i.v. (n = 11) on Day 14 or 15 postpartum. Jugular blood samples were collected at 15-min intervals for 2 hr before and 2.5 hr after NAL or saline. All cows received 3 ug gonadotropin releasing hormone (GnRH) at 2.5 hr post-NAL or -saline and blood collection was continued for 1 hr. Mean serum progesterone concentration was 0.33 +/- 0.2 ng/ml. Mean net energy balance for all cows was -5.5 +/- 0.6 Mcal/day. Naloxone caused a transient increase (P < 0.05) in serum LH concentrations in both primi- and multiparous cows within 45 min after administration. In contrast, serum LH concentrations remained unchanged in saline-treated cows. GnRH increased (P < 0.05) LH and there was no effect of treatment. These results suggest that modulation of LH secretion, at least in part, may be mediated via endogenous opioids in dairy cows before first postpartum ovulation.

Topics: Animals; Anovulation; Cattle; Female; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Multivariate Analysis; Naloxone; Narcotic Antagonists; Parity; Postpartum Period; Progesterone; Radioimmunoassay; Random Allocation

To investigate an involvement of endogenous opioids in the regulation of circannual changes in reproductive activity, effects of the opioid antagonist naloxone on the concentration of immunoreactive and bioactive luteinizing hormone (LH) in plasma were measured in mares during the anovulatory season. Naloxone (0.5 mg/kg i.v.) caused a significant increase (P < 0.05) in immunoreactive as well as bioactive LH concentration in plasma. The amplitude of the increase in LH concentrations measured with an in vitro bioassay was more pronounced than the amplitude of the increase in LH secretion determined by radioimmunoassay. This indicates that although in seasonal anovulatory mares the bioactivity of LH in plasma is low, highly bioactive LH is present in the anterior pituitary and can be released by naloxone. The LH response to naloxone did not depend on the degree of ovarian follicular activity. It can be concluded that a tonic opioid inhibition of LH release is present in mares during at least part of the anovulatory season and that endogenous opioids seem to be involved in the regulation of seasonal reproductive activity in the horse. In contrast to the situation during the breeding season, the opioid systems regulating LH release are activated independently of luteal progesterone.

Topics: Animals; Anovulation; Biological Assay; Estradiol; Female; Horses; Luteinizing Hormone; Naloxone; Ovarian Follicle; Pituitary Gland, Anterior; Progesterone; Radioimmunoassay; Seasons

The physiological amenorrhea occurring in suckled females has been associated with both hypopulsatile gonadotropin secretion and hyperprolactinemia. To test whether these phenomena are opiate mediated and whether these effects are dependent on the presence of ovaries, we studied six suckled, lactating cynomolgus monkeys, three with intact ovaries and three that were ovariectomized 14 days postpartum. Frequent blood sampling (every 15 min) was performed at approximately monthly intervals using chronic venous catheters accessed remotely via a jacket and tether system. Each monkey was administered saline or naloxone (2 mg bolus then 2 mg/h) by constant infusion, in alternating 6-h blocks. During saline infusions, PRL concentrations varied markedly in a diurnal pattern with concentrations varying from 30-70 micrograms/L during the day and from 100-200 micrograms/L during the night. In both gonadal intact and ovariectomized groups of monkeys naloxone dramatically suppressed and maintained PRL concentrations at less than 20 micrograms/L irrespective of the time of day or the order of administration. The effects of naloxone on gonadotropin concentrations were much less dramatic. In gonadal-intact monkeys, no effect of naloxone was seen on pulse frequency of either FSH or LH, or on mean LH concentration, and only a slight increase was noted in mean FSH concentrations. In ovariectomized monkeys, naloxone was also without effect on pulsatile LH secretion, although mean LH concentrations were slightly higher during naloxone infusions than during saline infusions (P less than 0.05). From these results, we conclude that opiate peptides are released in response to the suckling stimulus in the cynomolgus monkey and that they mediate the effects of suckling on PRL secretion in both gonadal-intact and agonadal cynomolgus monkeys. The lack of effect of opiate blockade on gonadotropin concentrations suggests that multiple pathways may be involved with the inhibition of the GnRH pulse generator during lactational anovulation.

Topics: Amenorrhea; Animals; Animals, Suckling; Anovulation; Endorphins; Female; Longitudinal Studies; Luteinizing Hormone; Macaca fascicularis; Naloxone; Ovariectomy; Pregnancy; Prolactin; Puerperal Disorders; Weaning

This study was designed to establish the normal pattern of serum progesterone and the origin of its secretion during the follicular phase of the normal menstrual cycle. In the first study, 12 normal women were studied on 3 occasions each at different times during a single follicular phase. Serum samples were collected every 10 min over 8 h, for 6 h before and 2 h after an injection of naloxone (5 mg iv). The mean serum progesterone remained constant (0.9 nmol/L) across the follicular phase until just before ovulation; individual subjects showed pulsatility of progesterone (1-6 pulses/6 h) but there was no relationship of this to LH pulsatility and no variation of progesterone pulsatility across the follicular phase. Naloxone caused an increase in the mean serum progesterone in the early follicular phase to 1.9 +/- 0.7 nmol/L and in the mid and late follicular phase to 2.1 +/- 0.7 nmol/L and 3.4 +/- 2.5 nmol/L, respectively. The second study was performed to assess the contribution of the residual corpus luteum and the developing follicle to the pulsatile secretion of progesterone. Seven anovulatory women with low levels of serum LH and absent LH pulsatility were studied before and after clomiphene (100 mg/day for 5 days) by collecting blood samples every 15 min for 6 h before GnRH (10 mg iv) and for 2 h afterwards. The anovulatory women had comparable mean serum concentration of progesterone (0.9 +/- 0.5 nmol/L) to normal women and similar frequency of progesterone pulsatility (2.1 +/- 1.1 pulses/6 h). After administration of clomiphene, there was no significant change in progesterone pulsatility (1.7 +/- 1.0 pulses/6 h) despite a substantial increase in LH pulsatility (from none to 3.0 +/- 1.0 pulses/6 h). There was no significant increase in serum progesterone after clomiphene or GnRH which both caused a substantial increase in serum LH. The third study involved eight normal women studied before and after treatment with dexamethasone (2 mg/day for 2 days) to assess the adrenal component of progesterone secretion. Blood samples were collected every 10 min for 6 h before and 2 h after naloxone (5 mg iv). Dexamethasone reduced serum progesterone to below assay sensitivity (less than 0.2 nmol/L) and obliterated progesterone pulsatility. The increase in serum progesterone and cortisol induced by naloxone was blocked by dexamethasone; the naloxone-induced rise of serum LH was not affected by dexamethasone. We conclude that neither the preceding corpus luteum

Topics: Activity Cycles; Adult; Anovulation; Dexamethasone; Estradiol; Female; Follicle Stimulating Hormone; Follicular Phase; Humans; Hydrocortisone; Luteinizing Hormone; Naloxone; Progesterone; Prolactin; Reference Values

Topics: Anovulation; Female; Gonadotropin-Releasing Hormone; Hormones; Humans; Naloxone; Opioid-Related Disorders; Thyrotropin-Releasing Hormone