Search PubMed⌕ Search

Biomedical subjects

J Rivier

Publications and source records attributed to J Rivier.

At least 325 records · Page 18Linked to original sources
PubMed1982

In vivo corticotropin-releasing factor-induced secretion of adrenocorticotropin, beta-endorphin, and corticosterone.

A 41-residue peptide purified as a corticotropin-releasing factor/beta-endorphin-releasing factor (CRF) in vitro was tested for its ability to stimulate the secretion of ACTH, beta-endorphin, and corticosterone in three animal groups: 1) unanesthesized rats bearing indwelling venous cannulae, 2) rats pretreated with chloropromazine plus morphine sulfate plus pentobarbital (CPZ-MS-Nb, and 3) rats with hypothalamic deafferentiations in the frontal and lateral retrochiasmatic areas. In all three bioassays iv administration of 0.1-10 micrograms CRF elicited a dose-related increase in plasma ACTH and beta-endorphin values over a 5- to 15-min period. Corticosterone secretion was also elevated but responded maximally with all doses of CRF tested. Pretreatment of CPZ-MS-Nb animals with 20 micrograms dexamethasone 4 h before assay abolished the CRF-induced hormone secretion. These data suggest that CRF may play a physiological role in the regulation of the hypothalamic-pituitary-adrenal axis.

Adrenocorticotropic Hormone↗
PubMed1982

Specific high affinity binding sites for somatostatin-28 on pancreatic beta-cells: differences with brain somatostatin receptors.

Saturable and high affinity binding sites have been obtained for an iodinated somatostatin-28 (SS-28) analog, [Leu8,D-Trp22,125I-Tyr25] SS-28, in a membrane preparation from hamster insulinoma, mainly composed of pancreatic beta-cells. Specific binding is maximal after 1 hour incubation at 22C and represents 65% of the total binding. KD for [Leu8,D-Trp22,Tyr25] SS-28 is 0.25 nM with the number of sites corresponding to 68 fmol/mg protein. The KD for SS-28 (1nM) is more than 5 times lower than that for SS-14. SS-28 analogs, such as [D-Trp22] SS-28 and analogs which selectively inhibit insulin release in vivo (Des-Asn5[D-Trp8,D-Ser13] SS-14 and Des-Asn19[D-Trp22,D-Ser27] SS-28), are the most potent compounds in this assay. C-terminal replacement of L-cysteine by D-cysteine reduces the apparent affinity of SS analogs. Unrelated peptides and the inactive analog Des-Trp8-SS-14 have no affinity for insulinoma binding sites. There are differences between the insulinoma SS binding sites and those monitored under similar conditions from rat cerebral cortex. In cerebral cortex, SS-14 and SS-28 have similar affinity for the binding sites, and the insulin selective analogs are less potent than SS-14. It is concluded that pancreatic beta-cells, as well as brain, possess high affinity binding sites for SS, but that they differ in some of their pharmacological properties.

Adenoma, Islet Cell↗
PubMed1982

Corticotropin-releasing factor: actions on the sympathetic nervous system and metabolism.

Corticotropin-releasing factor (CRF) injected into the brains of rats produces hyperglycemia and an increase in plasma concentrations of glucagon, epinephrine, and norepinephrine. Neither hypophysectomy nor adrenalectomy prevents CRF-induced hyperglycemia. However, a role of adrenal epinephrine release in mediating CRF-induced hyperglycemia is supported by the finding that the central nervous system-selective somatostatin analog, desAA1,2,4,5,12,13-[D-Trp8]somatostatin, totally prevents the elevation of plasma epinephrine and suppresses the rise of plasma glucose but does not alter the increase in plasma norepinephrine induced by CRF. Pretreatment with the ganglionic blocker chlorisondamine completely prevents the CRF-induced rises in plasma glucose, epinephrine, and norepinephrine. These results demonstrate that CRF acts within the brain to stimulate sympathetic outflow, which results in the development of hyperglycemia. In contrast to other peptides that act within the central nervous system, e.g. bombesin, TRF, and beta-endorphin, whose hyperglycemic actions depend exclusively on adrenal epinephrine secretion, CRF-induced hyperglycemia is secondary to the enhanced secretion of both epinephrine and norepinephrine.

Animals↗
PubMed1982

"Medical oophorectomy" using a long-acting GNRH agonist--a possible new approach to the treatment of endometriosis.

Five women with endometriosis were given a daily dose of a potent long-acting GnRH agonist, D-Trp6-Pro9-Net-LHRH (GnRH-A) for 28 days in an attempt to suppress ovarian estrogen secretion. The mean level of estradiol (E2) during sampling over 24 hours decreased (P less than 0.01) from 62 +/- 11 to 10 +/- 1 pg/ml at the end of treatment. Mean concentrations of androstenedione, testosterone, estrone and E2 on day 28 of therapy were similar to those measured in oophorectomized women. The level of FSH was decreased (P less than 0.001) during GnRH-a, whereas that of LH was significantly (P less than 0.001) increased, suggesting differing intracellular control mechanisms for release of the two gonadotropins. Desensitization of the pituitary was demonstrated at the end of treatment by a complete lack of acute response of FSH or LH to the daily dose of GnRH-a. "Medical oophorectomy" provides a new approach to the treatment of endometriosis.

Endometriosis↗
PubMed1982

Pituitary microadenomas causing Cushing's disease respond to corticotropin-releasing factor.

Corticotropin-releasing factor (CRF) was administered as an iv bolus to two young women with mild Cushing's disease shortly before and one week after successful transsphenoidal microadenomectomy. The dose of CRF (1 microgram/kg body weight) had previously been shown to stimulate increased plasma ACTH and cortisol in normal subjects. In the first patient, prior to surgery, there were brisk increases in ACTH and cortisol that exceeded those observed in normal subjects. ACTH rose by 2 min and reached a peak between 15-30 min. Cortisol increased by 10 min and peaked between 45-60 min. After surgery, at a time when plasma cortisol was maintained at similar levels with exogenous hydrocortisone, there was no plasma ACTH or LH, TSH and prolactin increased after administration of LRH and TRH, and GH increased in response to insulin-induced hypoglycemia. The second patient had higher basal plasma ACTH and cortisol than the first patient. CRF-induced increments in ACTH and cortisol were much less, but the time course was similar and peak levels attained were still higher than those in normal subjects. After surgery, at a time when plasma cortisol was maintained at a much lower level with exogenous hydrocortisone, there was no plasma ACTH or cortisol response. She had mild, transient diabetes insipidus. Basal levels of all other anterior pituitary hormones were normal. These results demonstrate that two microadenomas causing Cushing's disease were responsive to CRF in situ and suggest that CRF may be involved in the etiology and/or the responses to changes in plasma glucocorticoid concentrations observed in patients with Cushing's disease.

Adenoma↗
PubMed1982

Effects of synthetic corticotropin-releasing factor and dopamine on the release of immunoreactive beta-endorphin/beta-lipotropin and alpha-melanocyte-stimulating hormone from human fetal pituitaries in vitro.

The effects of synthetic corticotropin-releasing factor (CRF) and dopamine on immunoreactive beta-endorphin/beta-lipotropin (i beta-END/LPH) and alpha MSH release were studied in superfused human fetal pituitary glands. CRF (20 ng) stimulated the release of i beta-END/LPH in four anterior hemipituitaries from fetuses older than 20 weeks in gestation. There was no effect on three anterior hemipituitaries from fetuses of 19-20 weeks gestation. CRF had no effect on i beta-END/LPH or alpha MSH secretion from neurointermediate lobes regardless of fetal age. Dopamine (10(-6) M) had no effect on i beta-END/LPH or alpha MSH secretion from either anterior or neurointermediate lobes. The data suggest that anterior pituitary responsiveness to CRF develops at about 20 weeks gestation and that fetal neurointermediate lobe secretion of peptides is not regulated by CRF.

Corticotropin-Releasing Hormone↗
PubMed1982

Intermittent long-term administration of a potent gonadotropin-releasing hormone agonist in normal men.

The effects on pituitary-gonadal function of the potent gonadotropin-releasing hormone agonist D-trp6-pro9-n-ethylamide-LHRH (LRFA), 50 micrograms subcutaneously every 4th day for 10 weeks, were evaluated in seven normal men. A modest rise in mean serum LH levels was noted during the treatment period. Mean serum FSH levels were unchanged. Mean plasma testosterone (T) levels remained at 3.1 ng/ml or above. Sperm density during the control period varied widely within and between subjects, with a mean range of 69-137 million/ml. The mean sperm density fell to a nadir of 40 million/ml during treatment, but no consistent pattern was observed for each subject, with values varying between 4 and 368 million/ml. Elevated LH and T values were observed on eight and seven occasions, respectively, in five subjects, and corresponded to blood samples drawn 24 and 48 h after the last LRFA injection. Depressed T values were observed on 10 occasions in six patients, and in all but one, corresponded to blood drawn 72 and 96 h after the last injection. One subject had daily blood samples drawn at the start of and 4 weeks after beginning therapy. An agonist effect on LH, FSH, T, and estradiol was observed both times, although the effect was blunted on the second occasion. We conclude that treatment every 4 day with LRFA does not appear to be a promising regimen to induce consistent suppression of the pituitary-gonadal axis in man.

Adult↗
PubMed1981

Short-term treatment of idiopathic precocious puberty with a long-acting analogue of luteinizing hormone-releasing hormone. A preliminary report.

The uncoupling of pituitary stimulation and response observed in adults during administration of the luteinizing hormone-releasing hormone analogue, D-Trp6-Pro9-NEt-LHRH (LHRHa) suggested that this drug might be useful in treating precocious puberty. We treated five girls with idiopathic precocious puberty (ages two to eight) for eight weeks with daily subcutaneous injections of LHRHa. The patients had Tanner II to IV pubertal development, advanced bone age, an estrogen effect on vaginal smear, measurable basal gonadotropin levels with pulsed nocturnal secretion, and a pubertal gonadotropin response to LHRH. Irregular vaginal bleeding was present in three patients. LHRHa significantly decreased basal (P less than 0.025) and LHRH-stimulated (P less than 0.01) gonadotropin levels as well as serum estradiol (P less than 0.05). The vaginal maturation-index score, which reflects the estrogen effect, fell by 25 per cent. Eight weeks after stopping treatment, all hormonal values and the vaginal maturation index had returned to pretreatment levels. These favorable short-term results will need further study before the benefits and risks of chronic treatment with LHRHa can be adequately assessed.

Child↗
PubMed1981

Reversible inhibition of testicular steroidogenesis and spermatogenesis by a potent gonadotropin-releasing hormone agonist in normal men: an approach toward the development of a male contraceptive.

We studied the antifertility effects of a potent gonadotropin-releasing hormone agonist, D-Trp6-Pro9-N-ethylamide-LHRH (LHRHA) in eight normal men, who received daily subcutaneous injections for six to 10 weeks. Plasma testosterone levels fell substantially in all eight. Plasma 17-hydroxyprogesterone and serum estradiol-17 beta levels decreased concordantly with plasma testosterone. Impotence developed in five men between the sixth and seventh weeks of treatment, with resolution in each case within two weeks of stopping treatment. Serum gonadotropin levels also fell during treatment, briefly rebounding above basal levels when therapy ended. Sperm density and motility fell t a nadir during the seventh to 18th week after therapy. In six subjects sperm levels fell to 6 X 10(6) sperm per milliliter or less, and in the other two they decreased 70 and 86 per cent below basal mean values. Sperm density returned to pretreatment levels in all men during the 10-to-14-week recovery period. These results are consistent with LHRHA-induced pituitary "desensitization" but do not exclude a direct inhibitory effect of LHRHA on testicular steroidogenesis and spermatogenesis.

Adult↗
PubMed1981

Somatostatin-28, somatostatin-14 and somatostatin analogs: effects on thermoregulation.

Somatostatins, somatostatin-14, somatostatin-28, and desAA [D-Trp8]-somatostatin, with differential potencies, act in the brain to reverse chemical-induced hypothermia and to produce hyperthermia. Somatostatins are more potent and loger acting than prostaglandin E2 in producing hyperthermia. Hyperthermia, induced by somatostatins, is not prevented by previous treatment with the prostaglandin synthesis inhibitor indomethacin. Somtostatins given to obese ob/ob mice prevent development of lethal hypothermia and result in maintenance of euthermia. Continuous infusion of somatostatins results in desensitization to the hyperthermic effects of these peptides. Endogenous somatostatins may be involved in regulation of body temperature.

Animals↗