Biomedical subjects

W Vale

Publications and source records attributed to W Vale.

At least 199 records · Page 11Linked to original sources

PubMed1988

Gonadal and extragonadal expression of inhibin alpha, beta A, and beta B subunits in various tissues predicts diverse functions.

The S1-nuclease analysis was used to investigate the pattern of inhibin expression in the rat. In a first series of experiments, expression of the alpha, beta A, and beta B subunits of inhibin were monitored in various tissues from male and female rats. Two observations emerge from these studies. First, expression of inhibin subunits was found in gonadal and extragonadal tissues. In addition to the ovary and testis, inhibin alpha, beta A, and beta B RNAs were detected in the placenta, pituitary, adrenal, bone marrow, kidney, spinal cord, and brain. Detection of inhibin RNAs in the brain and spinal cord suggested that these subunits may exert neuroregulatory functions in the central and peripheral nervous systems. Furthermore, the presence of inhibin alpha and beta subunits in the placenta and the pituitary gland, two cell types that have clearly been shown to be regulated by exogenous inhibin, may reflect existing paracrine and/or autocrine processes active in these tissues. The second observation is that expression of inhibin subunit RNAs may vary by severalfold in a tissue-specific fashion. for example, alpha-subunit RNA levels are abundant in the gonads, whereas beta A-subunit RNA is predominant in the placenta and bone marrow. Finally, it is noted that expression of testicular inhibin RNA subunits decreases during sexual maturation. We conclude that the dimers comprised of inhibin subunits possess diverse functions and may act as growth/differentiation factors as well as a hormone.

Animals↗

PubMed1988

Interleukin 1 prevents loss of corticotropic responsiveness to beta-adrenergic stimulation in vitro.

Corticotropin (ACTH) secretion by the anterior pituitary is stimulated by catecholamines in vivo and in vitro. The nature of the response in vivo is controversial but appears to be mediated by beta-adrenergic receptors, whereas the response is dependent on alpha-adrenergic receptors in cultured anterior pituitary cells. In the present studies, by using a superfusion technique, we demonstrate that catecholamine stimulation of ACTH release from rat anterior pituitaries changes with time from a predominantly beta-adrenergic-mediated event to a predominantly alpha-adrenergic-mediated event. From 0 to 2 hr after initiating the superfusion, release of ACTH from anterior pituitary glands is stimulated up to 2.4-fold by the beta-adrenergic agonist l-isoproterenol. However, the ACTH secretory response to the alpha-adrenergic agonist l-phenylephrine is less than or equal to 5% of that to l-isoproterenol during the same time period. Beginning 2 hr after the start of the superfusion, the responsiveness to the beta-adrenergic agonist declines, and the response to the alpha-adrenergic agonist increases until, 10 hr after removal, greater than 95% of the catecholamine-inducible ACTH release is mediated by an alpha-adrenergic pathway. The addition of interleukin 1 alone to the medium from the beginning of the superfusion does not modify basal ACTH secretion rates and does not affect the acquisition of the response to phenylephrine. However, the presence of interleukin 1 does allow the maintenance of the full ACTH secretory response to isoproterenol. This effect of interleukin 1 is reversed by an interleukin 1 antagonist. These observations suggest an additional way in which immune regulators might interact with the hypothalamic-pituitary-adrenal axis.

Adrenergic alpha-Agonists↗

PubMed1988

Interaction between ethanol and stress on ACTH and beta-endorphin secretion.

The intraperitoneal infusion of ethanol (EtoH) (1 g/hr/kg body weight for 3 hr) to intact rats blunted the secretion of adrenocorticotropic hormone (ACTH) and beta-endorphin induced by a subsequent 10-min exposure to mild, inescapable electroshocks (1.5 mA; 2 sec; four shocks/min) or by corticotropin-releasing factor (CRF). Conversely, administration of the shocks for 3 hr diminished the pituitary response to an acute i.p. injection of EtoH. While we have previously shown (Rivier C, Vale W: Endocrinology 121:1320-1328, 1987) that prolonged stress induces a loss of pituitary responsiveness due to the depletion of pituitary ACTH stores, the infusion of EtoH did not cause statistically significant changes in pituitary ACTH content. In adrenalectomized rats, the infusion of EtoH caused an elevation of ACTH plasma levels that was significantly (p less than or equal to 0.01) larger than intact animals. These rats also showed a blunted pituitary response to the acute injection of CRF, possibly because they were already secreting ACTH at a maximal rate. These results support the hypothesis that CRF, stress, and alcohol do not potentiate each other on pituitary ACTH and beta-endorphin secretion.

Adrenalectomy↗

PubMed1988

Potent long-acting growth hormone releasing factor analogues.

Amidated fragments 1 to 29 of human growth hormone releasing factor, (GRF1-29NH2), were designed to encompass modifications that could prevent degradation by exopeptidases. The NH2-terminus was blocked by either N-methylation of Tyr1 or by introduction of NMeDAla2 while the COOH-terminus was blocked by an N-ethylamide. Other substitutions such as Nle in position 27 for methionine conferred stability toward air oxidation while Asn28, an amino acid substitution found in rat GRF, seemed to confer stronger binding affinity to the GRF receptor. Potency in vitro and duration of action in vivo of [NMeTyr1,Nle27,Asn28]hGRF1-29NHEt (4SG-29) were compared to those of hGRF1-40OH. 4SG-29 was found to be both ten times more potent than hGRF1-40)OH and exhibit significantly extended duration of action.

Amino Acid Sequence↗

PubMed1988

Inhibin: studies of stored and secreted forms by biosynthetic labeling and immunodetection in cultured rat granulosa cells.

The biosynthesis of inhibin in rat granulosa cells was studied by biosynthetic labeling, immunoblotting, and immunocytochemical techniques. Granulosa cells from immature hypophysectomized estrogen-treated rats were cultured in the presence of [35S]cysteine. Both conditioned media and cell extracts were subjected to immunoprecipitation with an antibody directed against the N-terminal 26 amino acids of the alpha-chain of porcine inhibin (pI alpha 1-26), followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fluorography. Treatment with FSH (100 ng/ml) and delta 4-androstenedione (10(-7) M) increased the secretion of 35S-labeled inhibin immunoreactivity by 2.6-fold over that in control cultures treated with androstenedione alone. The radiolabeled inhibin had mol wt (Mr) values of 45,000 and 30,000. Upon reduction, the 45,000 Mr polypeptide remained (with increased apparent Mr of 49,000), but the 30,000 Mr species disappeared with the concomitant appearance of two bands with 18,000 and 11,000 Mr. Competition studies with pI alpha 1-26 confirmed that these polypeptides were all related to inhibin. Furthermore, immunoblotting with an antibody directed against the porcine inhibin beta-A chain (pI beta A81-113) indicated that the 11,000 Mr peptide was the inhibin beta-A chain. Extracts of cells treated with FSH contained only a high Mr alpha-related species (Mr, 41,000 nonreduced; 49,200 reduced). The inhibin alpha antibody was also used to immunocytochemically stain cultured granulosa cells. Cells that had been treated with FSH or the adenyl cyclase activator forskolin (3 x 10(-5) M), but not untreated cells, exhibited positive staining. These results indicate that granulosa cells synthesize and store inhibin alpha-chain precursor with 49,000 Mr. Although some of the high Mr alpha-form was secreted, the majority of the alpha-subunit was processed to the 18,000 Mr form and dimerized with the 11,000 Mr beta-chain to form the mature inhibin dimer immediately before secretion. The cultured granulosa cells may provide a model for future studies on the hormonal regulation of inhibin alpha- and beta-gene expression as well as subunit dimerization and secretion.

Androstenedione↗

PubMed1988

Dissociation of the adrenocorticotropin secretory responses to corticotropin-releasing factor (CRF) and vasopressin or oxytocin by using a specific cytotoxic analog of CRF.

Control of ACTH secretion in the pituitary in the absence of target cells for CRF, the most potent ACTH secretagogue, was studied in dissociated bovine anterior pituitary cells treated with a potent selective cytotoxin. The cytotoxin is a conjugate of the CRF analog [Nle21,38, Arg36]rat (r) CRF and the plant toxin gelonin. Dissociated bovine anterior pituitary cells were pretreated with vehicle, 2 nM ovine CRF, 2 nM cytotoxic conjugate, or unconjugated [Nle21,38,Arg36]rCRF and gelonin in amounts equivalent to that of 2 nM cytotoxic conjugate for 12 h, then extensively washed and cultured for 3 days before acute secretion experiments. Unstimulated ACTH secretion was similar in all groups. ACTH secretion in response to CRF was attenuated by pretreatment with the cytotoxic conjugate; CRF (2.5 nM)-stimulated secretion was 7.0, 6.3, and 2.8 times the unstimulated rate in cells pretreated with vehicle, 2 nM CRF, or 2 nM cytotoxic conjugate, respectively. Likewise, the ACTH secretory response to a cAMP analog was attenuated by pretreatment with the conjugate; 8-bromo-cAMP (10 mM)-stimulated secretion was 6.8, 7.1, and 3.3 times the unstimulated rate in cells pretreated with vehicle, CRF, or conjugate, respectively. In contrast, the ACTH responses to vasopressin (VP) or oxytocin (OR) remained intact. VP stimulated the ACTH secretion rate by 4.2, 4.0, and 3.5 times, respectively, in the three groups. OT stimulated the ACTH secretion rate by 2.7, 2.6, and 2.3 times in the three groups. Pretreatment with the conjugate attenuated the response to CRF and VP in combination by the same amount as it attenuated the response to CRF alone. The ACTH secretory responses in cells pretreated with unconjugated [Nle21,38,Arg36]rCRF and gelonin were not different from responses in cells pretreated with vehicle. These results suggest that there is a separate mechanism or cell type for OT- and VP-stimulated ACTH secretion distinct from that responsible for the action of CRF on pituitary cells.

Adrenocorticotropic Hormone↗

PubMed1988

Age-dependent changes in physiological action, content, and immunostaining of inhibin in male rats.

We examined the role of endogenous inhibin in modulating FSH secretion in male rats during the infantile (days 10 to 21), juvenile (days 22 to 35), and pubertal (days 36 to 90) periods by 1) neutralization of endogenous inhibin using specific antibodies, 2) measurement of plasma and testicular levels of immunoreactive inhibin, and 3) immunohistochemical detection of testicular inhibin. In all studies, we used an antiserum against the first 26 N-terminal amino acids of the alpha-chain of porcine inhibin (anti-alpha-inhibin). Plasma immunoreactive inhibin levels were highest in young rats (8-15 days old), then decreased steadily with age. In addition, iv injection of the inhibin-alpha antiserum caused significant (P less than or equal to 0.01 or P less than or equal to 0.05) elevations in plasma FSH levels in male rats aged 10-24 days, whereas no significant (P greater than 0.05) changes occurred in older animals. In the testes, immunoreactive inhibin levels, expressed as femtomoles per mg wet weight, also declined with age. Inhibin immunostaining was most prominent in the Sertoli cells, with the greatest staining in the testes of 8 to 15-day-old rats. These results suggest that endogenous inhibin plays a physiological role in suppressing FSH secretion in infantile male rats, at an age when Sertoli cells contain the largest amount of this protein.

Aging↗

PubMed1988

Interaction between purified ovine inhibin and steroids on the release of gonadotropins from cultured rat pituitary cells.

Primary pituitary cell cultures derived from adult male rats were used to explore the interaction between purified 32K ovine inhibin and gonadal steroids on the modulation of basal and GnRH-stimulated secretion of FSH and LH. Purified o-inhibin was a potent inhibitor of basal FSH secretion (IC50 = 3.4 pM) and 10 nM GnRH-stimulated FSH and LH secretion (IC50 = 8.8 and 18.4 pM, respectively). Purified o-inhibin had no effect on basal LH secretion. In this system, the androgens testosterone, 5 alpha-dihydrotestosterone, and androstenedione slightly stimulated basal FSH secretion, and o-inhibin could reverse this stimulatory effect. By contrast, androgens suppress GnRH-stimulated FSH and LH secretion. In combination, androgens and o-inhibin provided greater inhibition of GnRH-mediated gonadotropin secretion than either did alone.

Androgens↗

PubMed1988

Effects of low dose ovine corticotropin-releasing hormone in humans: endocrine relationships and beta-endorphin/beta-lipotropin responses.

The effects of low doses (0.03 and 0.1 microgram/kg) of ovine CRH (oCRH) on plasma beta-endorphin/beta-lipotropin (beta End/beta LPH), ACTH, and corticosteroid levels were studied in normal men. The 0.03 microgram/kg oCRH dose produced a reproducible response, with a rapid increase in plasma oCRH to peak levels between 45 and 95 fmol/mL and an appropriate doubling of plasma peptide and corticosteroid concentrations. The relationship between the corticosteroid rise and the rapid beta End/beta LPH and ACTH declines suggested negative feedback by corticosteroids on the release of these pituitary products. Plasma oCRH levels were proportionate to those reported in studies using much higher oCRH doses, and produced plasma oCRH levels in the reported range for the hypophyseal portal circulation. Molecular sieving of the beta End-immunoreactive materials in basal and post-oCRH (0.1 microgram/kg) plasma samples revealed an average basal beta End to beta LPH ratio of 1:1.5; 15 min after oCRH stimulation the average ratio was 4:1. We conclude that a low (threshold) dose of oCRH can reliably stimulate POMC peptide secretion and may preferentially release beta End from the anterior pituitary.

Adrenal Cortex Hormones↗

PubMed1988

The dependency of bioactive follicle-stimulating hormone secretion on gonadotropin-releasing hormone in hypogonadal and cycling women.

An antagonist analog of GnRH, (Ac-delta 3-Pro1,p-F-D-Phe2,D-Trp3,6)GnRH (4F-antagonist), was administered to normal women and women with hypergonadotropic hypogonadism. Serum FSH levels were determined by both the granulosa cell aromatase bioassay and RIA. The constant infusion of 4F-antagonist (30 micrograms/kg.h) to the four hypogonadal women resulted in a more pronounced decline in bioactive FSH (62%) than in immunoreactive FSH levels (30%), and the FSH bioactive to immunoreactive ratio decreased significantly (P less than 0.05). Infusion of 4F-antagonist in normal women in the midfollicular phase revealed a similar pattern of suppression of bioactive (64%) and immunoreactive FSH (29%). When 4F-antagonist was administered sc at a dose of 80 micrograms/kg twice daily for 3 days to normal women in the midfollicular phase of their cycles, the bioactive FSH response was biphasic, with the maximal decrease on the second day, followed by return to basal levels on the third day. Correspondingly, there was a precipitous decline in serum estradiol (apparent demise of the dominant follicle), followed by a progressive rise in estradiol levels. Thus, in contrast to immunoreactive FSH levels, bioactive FSH more clearly reflects the biological action of FSH on the follicle in response to GnRH antagonist administration in women. The disparity in the quantitative decline between serum bioactive and immunoreactive FSH levels after presumed blockade of the GnRH receptor may reflect the microheterogeneity of the FSH molecule and suggests that alterations in the biological activity of secreted FSH may be GnRH dependent.

Adult↗

PubMed1988

Maintenance of the ratio of bioactive to immunoreactive follicle-stimulating hormone in normal men during chronic luteinizing hormone-releasing hormone agonist administration.

Chronic administration of LHRH agonist analogs to humans reduces gonadal function through pituitary desensitization. Serum immunoreactive gonadotropin levels are modestly reduced, whereas serum bioactive LH levels are drastically suppressed. The effects on bioactive FSH levels, however, are not known. In this study, serum bioactive FSH was measured using an in vitro granulosa cell aromatase bioassay in four normal men given a LHRH agonist, [D-Trp6,Pro9-NEt]LHRH (LHRHA; 500 micrograms/day for 16 weeks), by sc infusion and testosterone enanthate (TE; 100 mg, im every 2 weeks) and in five men given 500 micrograms/day LHRHA by daily sc injection for 20 weeks and TE (100 mg every 2 weeks) from weeks 10 through 20. During the first study, serum immunoreactive FSH levels (IR-FSH) decreased by 56.5 +/- 4.8% (+/- SEM), and serum bioactive FSH (Bio-FSH) level decreased by 57.6 +/- 6.4%. The ratio of Bio-FSH to IR-FSH did not change. During the second study, both serum IR-FSH and Bio-FSH levels followed a triphasic pattern, decreasing slightly but not significantly immediately after initiation of LHRHA administration, progressively increasing to a peak (P less than 0.5 vs, baseline) at week 10, and then, after addition of TE to this regimen, decreasing slightly again. The Bio-FSH to IR-FSH ratio, as in the first study, did not change. When serum obtained at week 10 during the second study, just before initiation of TE, was chromatographed on a Sephadex G-100 column, IR-LH eluted in two distinct peaks, while IR-FSH eluted as a single peak. These results demonstrate that in normal men chronic LHRHA administration alone for up to 10 weeks or LHRHA plus TE for up to 16 weeks does not alter the qualitative characteristics of secreted FSH, since there was no dissociation between serum IR- and Bio-FSH levels.

Adult↗

PubMed1988

Characterization of growth hormone-releasing hormone receptors in pituitary adenomas from patients with acromegaly.

GHRH receptors in pituitary adenoma cell membranes from five patients with acromegaly were characterized using [125I] [His1,Nle27]GHRH-(1-32)NH2 ([125I]GHRHa) as a ligand. Specific binding of [125I]GHRHa to adenoma cell membranes was maximal within 20 min at 24 C, remained stable for 60 min, and was reversible in the presence of 500 nmol/L human GHRH-(1-44)NH2 (hGHRH). The specific binding increased linearly with 10-160 micrograms cell membrane protein. This binding was inhibited by 10(-11)-10(-6) mol/L hGHRH in a dose-dependent manner, with an ID50 of 0.20 nmol/L, but not by 10(-7) mol/L vasoactive intestinal peptide, glucagon, somatostatin-14, somatostatin-28, TRH, LHRH, and CRH. The specific binding of [125I]GHRHa to the membranes was saturable, and Scatchard analysis of the data revealed an apparent single class of high affinity GHRH receptors in five adenomas from acromegalic patients; the mean dissociation constant was 0.30 +/- 0.07 (+/- SE) nmol/L, and the mean maximal binding capacity was 26.7 +/- 7.0 (+/- SE) fmol/mg protein. In three nonfunctioning pituitary adenomas, GHRH receptors were not detected. The plasma GH response to hGHRH (100 micrograms) injection was studied in four acromegalic patients before surgery. Plasma GH levels increased variably in response to hGHRH injection in all four patients. However, there was no correlation between the characteristics of the tumor GHRH receptors and plasma GH responsiveness in these patients. We conclude that pituitary GH-secreting adenomas have specific GHRH receptors. Exogenously administered GHRH presumably acts via these receptors, but the variations in plasma GH responsiveness to hGHRH in these patients cannot be directly related to the variations in binding characteristics of the GHRH receptors on the GH-secreting adenoma cells.

Acromegaly↗

PubMed1988

Evidence of differential control of FSH and LH secretion by gonadotropin-releasing hormone (GnRH) from the use of a GnRH antagonist.

The differential regulation of immunoactive FSH and LH secretion by endogenous GnRH was studied using a GnRH antagonist, [Ac-D2Nal1,D4FPhe2,DTrp3,DArg6]GnRH (the NAL-ARG antagonist), in normal women in the early follicular phase of the menstrual cycle, and their responses were compared to those in two groups of control women. Pulsatile LH secretion was examined as an index of the completeness of blockade of endogenous GnRH secretion. There was a dose-dependent decrease in both the frequency and amplitude of LH pulses. At the highest dose, LH pulses were completely abolished within 20 min after sc administration of the GnRH antagonist and for a minimum of 8 h in all women. The mean plasma LH levels were reduced within the first 4 h after antagonist administration at all doses (P less than 0.001). The duration of LH suppression was influenced by antagonist dose, with a continued effect 24 h after administration of the 500 micrograms/kg dose only. The maximum degree of LH suppression was 40% after 50 micrograms/kg (n = 6), 60% after 150 micrograms/kg (n = 6), and 59% after 500 micrograms/kg (n = 5). In contrast, plasma immunoreactive FSH levels did not change after these doses of the NAL-ARG GnRH antagonist. The maximum degree of FSH suppression was 16%, and the changes in plasma FSH concentrations were not dose dependent. Serum antagonist concentrations rose within 30 min after its administration to mean peak levels of 7.5 +/- 2.1 (+/- SE), 20.4 +/- 6.1, and 151 +/- 21 ng/mL after the 50, 150, and 500 micrograms/kg doses, respectively. The half-time of the disappearance of the NAL-ARG GnRH antagonist from plasma was 8.8 +/- 1.5 h. While there were no effects of antagonist administration on hematological, hepatic, or renal function, three women developed urticaria distant from the site of injection when administered the highest dose. We conclude that blockade of GnRH receptors by a GnRH antagonist 1) effectively antagonizes the action of GnRH, as assessed by its ability to block pulsatile LH secretion and reduce mean plasma LH levels; and 2) inhibits LH release to a considerably greater degree than FSH release, providing further evidence of possible GnRH-independent FSH secretion.

Adult↗

PubMed1988

Rapid changes in the expression of inhibin alpha-, beta A-, and beta B-subunits in ovarian cell types during the rat estrous cycle.

Distributions of inhibin alpha-, beta A-, and beta B-subunits in different ovarian compartments were studied in cycling female rats by in situ hybridization with complementary RNA probes and using immunohistochemical localization with antibodies selective for each inhibin subunit. Consistent with earlier studies showing inhibin production by granulosa cells of maturing follicles, we also detected mRNAs for inhibin alpha-, beta A-, and beta B-subunits in granulosa cells of these follicles. However, based on immunohistochemistry and in situ hybridization, we found that inhibin alpha- is not only expressed in granulosa cells of mature follicles but in follicles at all stages of maturation, including primary to tertiary follicles. A number of primordial follicles also contained alpha mRNA and immunodetectable alpha-subunit. Interestingly, theca interna and interstitial gland cells contained inhibin alpha mRNA and alpha-subunit. Low levels of inhibin alpha immunoreactivity as well as specific hybridization to the complementary inhibin alpha mRNA probe were observed in newly formed luteal tissue. beta-Subunits, on the other hand, were detected exclusively in granulosa cells of healthy tertiary follicles. The changes in expression of inhibin alpha-, beta A-, and beta B-subunits were more pronounced during the follicular phase of the cycle: inhibin alpha reached its highest level in granulosa cells, theca interna, and interstitial gland cells a few hours after the LH/FSH surge, while at the same time the beta-subunits decreased dramatically in granulosa cells of mature follicles. Immediately before ovulation (estrus 0200 h), the alpha-subunit sharply declined in preovulatory follicles and was present mainly in granulosa cells from nonovulatory follicles at various stages of maturation. At that time, the beta A- and beta B-subunits could not be detected in preovulatory follicles but were localized mainly in small tertiary follicles (less than 300 microns). Unlike for the alpha- and beta B-subunits, beta A mRNA and immunoreactivity was present in large tertiary follicles (approximately 600 microns) immediately before ovulation. The present findings support the hypothesis that a decrease in inhibin production could be responsible for the secondary FSH surge observed early on estrus. This could be initiated by a change in the ratios of activin-inhibin production by decreasing first, the levels of beta-subunits, second, the levels of alpha-subunit, and third, by a resurgence of activin A produced mainly by granulosa cells from large tertiary follicles.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1988

Use of osmotic pumps for subcutaneous infusion of growth hormone-releasing factors in steers and wethers.

Osmotic pumps were evaluated for 7-d delivery of growth hormone-releasing factor (GRF). In Exp. 1, 12 steers weighing 253 kg received hGRF(1-29)NH2 in H2O at rates of 0, 3, 30 and 300 pmol.h-1.kg-1. Pumps were implanted s.c. on d 0 and removed at 1200 on d 7. Blood samples were drawn at 20-min intervals from 0800 to 1200 on d -1, 1, 3, 5, 7 and 9. Growth hormone levels were not altered by GRF treatment (P greater than .05). Solubility and volume limitations render hGRF(1-29)NH2 delivery via osmotic pumps problematical. Flow rate and duration of release of dimethyl sulfoxide (DMSO):H2) (1:1) from osmotic pumps incubated in vivo and in vitro were found to be consistent with manufacturer's specifications. Two hGRF(1-29) analogues, Ro23-7863 and 4SG-29, were dissolved in DMSO:H2O. In Exp. 2, six 222-kg steers had pumps implanted and blood samples were taken as in Exp. 1. Three steers received each analogue at a rate of 300 pmol.h-1.kg-1. Analogues had similar GH-releasing ability and GH levels differed (P less than 0.001) among days, being approximately fourfold higher on d 3, 5 and 7 than on d -1, 1 and 9. Residual analogue solutions retained full bioactivity after 7-d implantation, and in vitro biopotencies of Ro23-7863 and 4SG-29 were similar (Exp. 3). In Exp. 4, 15 wethers (means = 31.3 kg) received osmotic pumps delivering 0, 3, 15, 75 and 300 pmol.h-1.kg-1 Ro23-7863 in DMSO:H2O for 7 d. Lambs were bled at 0800 and 1400 from d -1 to 8. The latter two doses increased (P less than .01) mean GH levels 2.7- and 4.3-fold over those in control animals during the treatment period. Results demonstrate that increased GH secretion can be elicited in steers and wethers for 1 wk by continuous s.c. infusion of GRF analogues utilizing osmotic pumps.

Animals↗

PubMed1988

Growth hormone-releasing factor on growth hormone secretion in prepubertal calves.

The effects of iv administration of growth hormone-releasing factor (GRF) on growth hormone (GH) release and on nitrogen metabolism were measured in prepubertal calves. Crossbred beef heifers (111 kg) were used in a Latin square design to test the effects of 0, 0.01, 0.033, 0.067, and 0.1 microgram human pancreatic (hp) GRF [hpGRF (1,40)OH]/kg body wt on plasma GH concentrations. When they were given doses of 0.067 and 0.1 microgram hpGRF/kg body wt, plasma GH increased (P less than 0.05) within 5-15 min, compared with injections of control buffer, and then returned to preinjection concentrations. The response to 0.067 microgram hpGRF/kg body wt every 3 hr for 42 hr was studied in five heifers (137 kg body wt). The animals responded to 50% of the GRF injections with an increase in plasma GH during every 6-hr period measured. Nitrogen retention, hormone concentrations, and weight gain were measured in five bull calves (90 kg body wt) administered 0 or 0.067 microgram Nle rat hypothalamic GRF (1,29)NH2/kg body wt every 4 hr for 10 days. Metabolic parameters were interpreted to indicate an anabolic response to GRF even though increases of 16% in nitrogen retention, 23% in plasma somatomedin C concentrations, and 36% in weight gain with pulsatile GRF treatment were variable and statistically similar to those of controls. These results indicate that GRF induces peak GH secretion within 15 min in prepubertal calves and that calves can respond to multiple injections of GRF with an increase in plasma GH.

Animals↗

PubMed1987

Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor.

There is now evidence that the immune system, during times of infectious challenge, can stimulate the secretion of glucocorticoids, the adrenal steroids that mediate important aspects of the response to stress. Specifically, secretion of interleukin-1 (IL-1), a monocyte lymphokine secreted after infection, appears at least in part responsible for this effect. Glucocorticoids are secreted in response to a neuroendocrine cascade involving, first, the brain, then the pituitary, and finally the adrenal gland. In this report, human IL-1 is shown to activate the adrenocortical axis at the level of the brain, stimulating the release of the controlling hormone corticotropin-releasing factor (CRF) from the hypothalamus. Infusion of IL-1 induced a significant secretion of CRF into the circulation exiting the hypothalamus, whereas immunoneutralization of CRF blocked the stimulatory effect of IL-1 on glucocorticoid secretion. IL-1 appeared to have no acute direct stimulatory effects on the pituitary or adrenal components of this system. Furthermore, IL-1 did not cause a nonspecific release of other hypothalamic hormones. Thus, the lymphokine acts in a specific manner to activate the adrenocortical axis at the level of the brain; this effect appears to be unrelated to the known pyrogenic effects of IL-1 within the hypothalamus.

Adrenal Cortex↗

PubMed1987

Cocaine stimulates adrenocorticotropin (ACTH) secretion through a corticotropin-releasing factor (CRF)-mediated mechanism.

Cocaine was injected intravenously to non-anesthetized, freely moving adult male rats and caused dose-dependent elevations in plasma adrenocorticotropin (ACTH) levels. The observation that this stimulatory effect was completely abolished by pretreatment with a corticotropin-releasing factor (CRF) antiserum, coupled with the lack of effect of cocaine on ACTH secretion by cultured pituitary cells, suggests that cocaine acts within the brain to release endogenous CRF.

Adrenocorticotropic Hormone↗