Effects of morphine and naloxone on phasic release of luteinizing hormone and follicle-stimulating hormone.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J Meites.
Explore the source record for details and available documents.
In general, the endogenous opioid peptides (EOP), morphine (MOR), and related drugs exert similar effects on acute release of pituitary hormones. Thus administration of opiates produces a rapid increase in release of prolactin (PRL), growth hormone (GH), adrenocorticotropin (ACTH), and antidiuretic hormone (ADH), and a decrease in release of gonadotropins and thyrotropin (TSH). Although not yet fully established, there is growing evidence that the EOP participate in the physiological regulation of pituitary hormone secretion. Thus naloxone (NAL), a specific opiate antagonist, has been shown to reduce basal serum levels of PRL and GH, and to elevate serum levels of LH and follicle stimulating hormone in male rats. Other reports have shown that NAL can inhibit the stress-induced rise in serum PRL, raise the castration-induced increase in serum LH to greater than normal castrate values, and counteract the inhibitory effects of estrogen and testosterone on LH secretion. Opiates appear to have no direct action on the pituitary, but there is evidence that they can alter activity of hypothalamic dopamine and serotonin in modulating secretion of pituitary hormones.
The relation of neuroendocrine functions to the reproductive decline was compared in human subjects and in rats of both sexes. The ovaries of rats remain potentially functional throughout the animal's life span, but cease to exhibit regular 4- or 5-day cyclic changes at about midelife. The loss of estrous cycles is believed to be due primarily to changes in hypothalamic neurotransmitters that lead to failure to exhibit cyclic surges in release of hypothalamic luteinizing hormone-releasing hormone and pituitary gonadotropins. Menstrual cycles normally cease in women between 40 and 50 years of age, primarily because the ovaries decline in their capacity to respond to gonadotropic stimulation with adequate production of estrogen and progesterone, and by ovulation, which in turn leads to increased gonadotropin secretion. In aging male rats, testosterone secretion by the testes decreases due to reduced stimulation by gonadotropins, in turn caused by decreased hypothalamic stimulation. Elderly men have been reported to show a reduction in testosterone and sperm production, accompanied by an increase in gonadotropin secretion, but more recent work in healthy, active men showed no increase in testosterone secretion with age.
Female Sprague-Dawley rats with established 7, 12-dimethylbenz(a)anthracene-induced mammary tumors were given daily s.c. injections of 50 microgram dexamethasone per rat, 0.5 mg haloperidol per kg, or both for 3 weeks. Control rats received the injection vehicles only. Mammary tumor growth was measured at weekly intervals for 21 days, and blood was collected on Days 10 and 21 of treatment for assay of prolactin. Dexamethasone produced significant regression of mammary tumors and reduced serum prolactin levels, whereas haloperidol significantly increased mammary tumor growth and greatly elevated serum prolactin levels. When dexamethasone and haloperidol were injected together, there was significant regression of mammary tumors despite markedly elevated serum prolactin levels. No significant differences in specific prolactin binding to membrane preparations of mammary tumors from these animals were observed in any treatment group. These results indicate that dexamethasone, a synthetic glucocorticoid, can directly inhibit mammary tumor growth in the presence of elevated serum prolactin levels produced by haloperidol, and this inhibition is not due to a reduction of prolactin binding sites in the tumor tissue.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Prior to the cessation of reproductive cycles, older female rats exhibit irregular and prolonged cycles due to alterations in the hypothalamic-pituitary-ovarian axis. In order to evaluate the age-related changes in the ovary, the histology, and estradiol, testosterone and progesterone concentrations within the ovaries of mature regular cycling (4--5 mo. old) and older irregular cycling (10--11 mo. old) rats were examined. At estrus, the number of non-atretic growing follicles (150--300u in diameter) was greater in the mature than in the older rats (18 +/- 1.5 vs 4.5 +/- 1.4). However, the number of preovulatory follicles on proestrus did not differ (6.0 +/- 1.2 vs 5.5 +/- 0.6). Estradiol, testosterone and progesterone concentrations on proestrus in mature rats averaged 38.8 pg, 56.1 pg, and 1.0 ng/ml of ovary, respectively. In the older proestrous rat, only estradiol was altered, increasing to 124.3 pg/mg. In addition, many of the preovulatory follicles within the aged ovary were larger (greater than 600u in diameter) than those within the mature ovary. On the day of estrus virtually all preovulatory follicles ovulated in the mature rat, whereas large follicles, less than or equal to 600u in diameter, remained in the older ovary. In addition, estradiol levels remained elevated and ovarian cysts were observed in the aged ovary. Thus, in the older irregular cycling rat, 1) pre-ovulatory follicles develop, but many do not ovulate; 2) these non-ovulatory follicles form ovarian cysts which remain within the ovary. The number of cysts may increase with age until a polycystic ovary develops and the rat enters a constant estrous state.
Explore the source record for details and available documents.
The effects of morphine (M) and naloxone (N) on serum levels of luteinizing hormone (LH) and prolactin (PRL) in prepubertal male and female rats were investigated. N raised serum LH concentrations in female rats at 10, 15, 20, 25 and 30 days of age, but increased serum LH levels in male prepubertal rats only at 30 days of age. M significantly depressed serum LH values in both sexes only at 15 days of age. M increased serum PRL levels in immature rats of both sexes in all age groups, except in 25-day-old males, whereas N decreased serum PRL only in 25-day-old male rats. These data show that there are differences in the pituitary LH and PRL responses to M or N of immature as compared to the responses previously reported in mature rats, and suggest that the endogenous opioid peptides may have a role in regulating LH and PRL secretion in immature rats.
The effect of T4 on specific PRL binding in the kidneys and adrenals was measured in intact, hypophysectomized, and thyroidectomized male rats. PRL binding in the kidneys was reduced from 12.1 +/- 1.1% in the intact group to 4.5 +/- 0.5% after hypophysectomy; 4-day replacement with T4 returned PRL binding to intact values. T4 administered to intact rats significantly increased PRL binding above intact values. Thyroidectomy reduced PRL binding in the kidneys from 14.9 +/- 1.2% to 7.0 +/- 0.6%, and T4 treatment restored PRL binding to intact values. PRL binding was measured at 2, 3, 5, 7, and 10 days after thyroidectomy in kidneys and found to decrease progressively from 8.2+/-0.5% in the intact rats to 2.3+/-0.3% on day 10. A single injection of T4 doubled PRL recetor binding in kidneys of thyroidectomized rats at 12 h and returned binding to intact levels at 24 h. In contrast to the effects of T4 on kidney PRL binding, adrenal PRL binding was only slightly altered by thyroidectomy and T4. These results suggest that T4 has a specific role in regulating PRL receptors in the kidneys but not in the adrenals. Since PRL receptors in the adrenals were only slightly altered by thyroid status, it is believed that the changes in kidney receptors represent a specific rather than a general metabolic effect of T4.
Female Sprague-Dawley rats, weighing 200--225 g, were ovariectomized and, 10 days later, were given a single sc injection of 10 micrograms estradiol benzoate/100 g BW. Three days after estradiol benzoate treatment, animals received 50 micrograms progesterone (P)/100 g BW, resulting in a surge in LH release 7 and 9 h later. To determine the locus of the noradrenergic component of the P-induced LH surge, 6-hydroxydopamine (6-OH-DA), a neutrotoxin, was implanted into either the suprachiasmatic region or the median eminence (ME) 24 h before P administration. An implant of 6-OH-DA in the suprachiasmatic region decreased anterior hypothalamic norepinephrine concentration by 83%, anterior hypothalamic dopamine concentration by 24%, and eliminated the P-induced LH surge. ME implant of 6-OH-DA decreased norepinephrine concentration by 57% without affecting dopamine concentration, but was unable to alter the P. induced LH surge. These results indicate that the anterior hypothalamic noradrenergic system is necessary for the P-induced LH surge in ovariectomized rats and that noradrenergic nerve terminals in the ME are not involved in this process.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Serum testosterone levels, testicular LH binding and the spermatogenic cycle were analyzed in rats 4 and 22 mo of age. With age, serum testosterone levels decreased from 3.2 to 0.63 ng/ml serum. There was no age related decline in testicular LH binding or changes in the spermatogenic cycle.
The effects of bilateral adrenalectomy or estradiol benzoate treatment were observed on growth of 7,12-dimethylbenz(a)-anthracene-induced mammary tumors during postpartum lactation. In the control and estradiol benzoate-treated postpartum lactating rats, the mammary tumors decreased approximately 40% in size by Day 5 postpartum and continued to regress to 50% of their average original diameter by Day 25 postpartum. Adrenalectomy on Day 3 postpartum prevented mammary tumor regression and resulted in renewed mammary tumor growth. By Day 10 postpartum, average mammary tumor size in the adrenalectomized rats reached prepartum diameter and continued to increase in size until Day 25. Although serum prolactin concentrations were significantly higher in the lactating rats with mammary tumors than in the nonlactating rats with mammary tumors, there were no significant differences in serum corticosterone values. Adrenalectomy resulted in a significant increase in serum prolactin levels and in a marked fall in serum corticosterone levels. It is concluded that in rats adrenocortical activity is primarily responsible for reduced mammary tumor growth during postpartum lactation.