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Biomedical subjects

W Vale

Publications and source records attributed to W Vale.

At least 379 records · Page 21Linked to original sources
PubMed1982

Corticotropin-releasing factor: effects on the sympathetic nervous system and oxygen consumption.

Corticotropin-releasing factor administered intracerebroventricularly produces prolonged elevation of plasma concentration of epinephrine, norepinephrine and glucose. These hormonal changes are associated with an increase in motor activity and oxygen consumption. No change in body temperature is observed. CRF produces changes in animal physiology that are similar to those observed in response to stress.

Animals↗
PubMed1982

Pituitary somatostatin receptors: dissociation at the pituitary level of receptor affinity and biological activity for selective somatostatin analogs.

High affinity and saturable binding of [125I-Tyr11]somatostatin (SS) is described in membrane homogenates from a pituitary transplantable tumor (GH4C1) rich in somatotrophs (KD for SS = 0.67 nM; Bmax = 30 fmol/mg protein). Binding characteristics and pharmacology are similar to those measured on normal pituitary membranes. The potency of various SS analogs highly correlates with that measured in in vitro bioassay for growth hormone. This suggests that those GH4C1 membranes are a good model for SS receptors on somatotrophs. Interestingly however, analogs in which the Asn5 is deleted (Des-Asn5) or D-Ser replaces Ser13 show dissociated potencies between the various assays: [D-Ser13] analogs are more potent in pituitary than in GH4C1 membranes binding assay. Des-Asn5-modified analogs are much more potent in both pituitary binding assays than in the bioassay. This could reflect a multiplicity of SS receptor subtypes in pituitary.

Animals↗
PubMed1982

Comparison of the biologic actions of corticotropin-releasing factor and sauvagine.

Corticotropin-releasing factor (CRF), a peptide isolated from ovine hypothalamus, and sauvagine, a peptide isolated from frog skin, share significant structural homology and elicit a number of similar biological responses. CRF is more potent than sauvagine in stimulating pituitary ACTH secretion. Sauvagine, however, is 5-10 times more potent than CRF to act within the brain to increase plasma levels of catecholamines and glucose and to elevate mean arterial pressure. Sauvagine is likewise more potent than CRF to act outside the brain to increase superior mesenteric artery flow and plasma glucose concentrations and to decrease mean arterial pressure. CRF and sauvagine produce important effects representative of biologically active peptides.

Adrenocorticotropic Hormone↗
PubMed1982

Introduction of rat growth hormone gene into mouse fibroblasts via a retroviral DNA vector: expression and regulation.

We have introduced the rat growth hormone gene into mouse fibroblasts via a retroviral DNA vector. The ability of the viral DNA to induce foci in the recipient cells was used as a dominant selection marker. Several copies of rat growth hormone DNA were integrated in the mouse cells. The transformed mouse cells expressed rat growth hormone-specific mRNA and secreted mature rat growth hormone. In rat cells, the expression of this gene is regulated by glucocorticoids. We demonstrate that hormone-dependent regulation transfers with the clone and thus appears to be an intrinsic property of the gene or its RNA products.

Animals↗
PubMed1982

Direct inhibition of testicular steroidogenesis and gonadotrophin receptor levels by [(imBzl)-D-His6, Pro9-NEt]GnRH and [D-Trp6, Pro9-NEt]GnRH, potent agonists of GnRH.

The effects of [(imBzl)-D-His6, Pro9-NEt]GnRH and [D-Trp6, Pro9-NEt]GnRH on testicular function in rats was evaluated. In adult rats the administration of 0.01, 0.1 or 10 micrograms of either agonist induced rapid increases in serum LH, FSH and testosterone (T) levels which started to decline within several hours. Both agonists caused a decrease in testicular LH and FSH receptor concentrations. The testicular FSH receptor concentration started to decline earlier than the LH receptor concentration but, both reached their lowest levels by day 2 after the administration of the agonists. The recovery of FSH receptor content was slower than that of LH. The extrapituitary effects of the 2 agonists were investigated in immature hypophysectomized animals. Administration of hCG (5 IU daily) to hypophysectomized rats for 5 days caused an increase in serum T levels. Concomitant administration of either of the agonists (10 micrograms) inhibited the steroidogenic action of hCG. Administration of the agonists alone caused a reduction in testicular LH receptor concentration in hypophysectomized rats. Treatment of the hypophysectomized rats for 0-4 days suggested that the direct antitesticular action of the agonists requires 1-2 days to become evident.

Animals↗
PubMed1982

Somatotroph hyperplasia. Successful treatment of acromegaly by removal of a pancreatic islet tumor secreting a growth hormone-releasing factor.

A 21-yr-old woman with Turner's syndrome presented with signs and symptoms of acromegaly. The serum growth hormone (GH) (95+/-9.4 ng/ml; mean+/-SEM) and somatomedin C (11 U/ml) levels were elevated, and an increase in GH levels after glucose instead of normal suppression, increase after thyrotropin-releasing hormone (TRH) administration instead of no change, and decrease after dopamine administration instead of stimulation were observed. The pituitary fossa volume was greater than normal (1,440 mm(3)) and the presence of a pituitary tumor was assumed. After tissue removal at transsphenoidal surgery, histological study revealed somatotroph hyperplasia rather than a discrete adenoma. Postoperatively, she remained clinically acromegalic and continued to show increased GH and somatomedin levels. A search was made for ectopic source of a growth hormone-releasing factor (GRF). Computer tomographic scan revealed a 5-cm Diam tumor in the tail of the pancreas. Following removal of this tumor, serum GH fell from 70 to 3 ng/ml over 2 h, and remained low for the subsequent 5 mo. Serum somatomedin C levels fell from 7.2 to normal by 6 wk postoperatively. There were no longer paradoxical GH responses to glucose, TRH, and dopamine. Both the medium that held the tumor cells at surgery and extracts of the tumor contained a peptide with GRF activity. The GRF contained in the tumor extract coeluted on Sephadex G-50 chromatography with rat hypothalamic GH-releasing activity. Stimulation of GH from rat somatotrophs in vitro was achieved at the nanomolar range, using the tumor extract. The patient's course demonstrates the importance of careful interpretation of pituitary histology. Elevated serum GH and somatomedin C levels in a patient with an enlarged sella turcica and the characteristic responses seen in acromegaly to TRH, dopamine, and glucose do not occur exclusively in patients with discrete pituitary tumors and acromegaly. This condition can also occur with somatotroph hyperplasia and then revert to normal after removal of the GRF source. Thus, in patients with acromegaly a consideration of ectopic GRF secretion should be made, and therefore, careful pituitary histology is mandatory. Consideration for chest and abdominal computer tomographic scans before pituitary surgery, in spite of their low yield, may be justified.

Acromegaly↗
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

Interaction of gonadotropin-releasing hormone agonist and antagonist with progesterone, prolactin, or human chorionic gonadotropin during pregnancy in the rat.

Two GnRH analogs, one agonist and one antagonist, have been administered to pregnant female rats with or without concomitant treatments with progesterone (Po), PRL, or hCG. During the first week of gestation, Po was consistently capable of totally reversing the deleterious effect of the agonist, while PRL and hCG were slightly less effective. During the second week of pregnancy, only Po and hCG were effective. When the antagonist was injected during either the first or second week after mating, both Po and hCG could prevent the abortifacient action of the analog, while PRL was without effect. These data suggest that the antigestational properties of gonadotropin-releasing hormone agonists are at least partially mediated through inhibition of PRL secretion, while those of gonadotropin-releasing hormone antagonists do not appear to be. Additionally, hCG as well as Po proved capable of counteracting the antigonadal effects of both classes of analogs.

Animals↗
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

Presence of corticotropin releasing factor-like immunoreactivity in hypophysial portal blood.

Hypophysial protal blood was collected from pentobarbital anesthetized male rats, and the content of corticotropin releasing factor-like immunoreactivity (CRF-LI) was measured using an RIA developed for synthetic ovine CRF. The concentration of CRF-LI in portal plasma was 104.9 +/- 9.7 pM. This concentration is in the range which has been shown to stimulate ACTH and beta-endorphin secretion in vitro. These data support the hypothesis that a molecule with the same or similar structure as synthetic ovine CRF is a physiologically significant hypothalamic releasing factor.

Adrenocorticotropic Hormone↗
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↗