Biomedical subjects

W Vale

Publications and source records attributed to W Vale.

At least 307 records · Page 17Linked to original sources

PubMed1984

Arginine vasopressin potentiates adrenocorticotropin release induced by ovine corticotropin-releasing factor.

Arginine vasopressin (AVP) stimulates ACTH release in man and acts synergistically with synthetic ovine corticotropin-releasing factor (oCRF) in vitro. This study was designed to examine in man the combined effects of synthetic AVP (10 U intramuscularly) and oCRF (1 micrograms/kg intravenously) on ACTH release. Five normal male volunteers participated in five separate experiments: (a) AVP alone; (b) oCRF alone; (c) AVP followed by oCRF 15 min later; (d) simultaneous AVP and oCRF; and (e) insulin-induced hypoglycemia. Plasma immunoreactive ACTH (IR-ACTH) and IR-cortisol were measured for 4 h after injection of each hormone; basal levels for all subjects were less than or equal to 9 +/- 1.2 pg/ml and 4.9 +/- 0.4 micrograms/dl (mean +/- SE), respectively. AVP and oCRF, when given individually, caused rapid rises in IR-ACTH to similar peak levels of 25 +/- 6.6 and 33 +/- 4.6 pg/ml, respectively. AVP given 15 min before oCRF caused a 2.6-fold potentiation of the oCRF response, with a peak IR-ACTH of 85 +/- 4.6 pg/ml. AVP given at the same time as oCRF produced a fourfold potentiation of the peak IR-ACTH response to 132 +/- 11 pg/ml. These ACTH responses were far greater than those previously observed after 30-fold greater doses of oCRF alone. By way of comparison, insulin-induced hypoglycemia caused a peak IR-ACTH of 169 +/- 20 pg/ml. IR-ACTH returned to base line at 60-90 min after AVP alone, whereas the prolonged effect of oCRF was apparent whether it was given alone or in combination with AVP. The mean peak IR-cortisol responses to AVP, oCRF, and AVP given 15 min before oCRF were similar (16.5 +/- 0.9, 16.4 +/- 2.3, and 18.5 +/- 0.8 micrograms/dl, respectively), but the peak IR-cortisol responses to AVP and oCRF given simultaneously and to insulin-induced hypoglycemia were 1.5 and 1.7 times greater, respectively. IR-cortisol returned to base line within 2-3 h after AVP alone, but remained elevated for at least 4 h after oCRF alone or in combination with AVP. These results indicate that AVP acts synergistically with oCRF to release ACTH in man and suggest that AVP may play a physiologic role in modulating the ACTH response mediated by corticotropin-releasing factor.

Adrenocorticotropic Hormone↗

PubMed1984

Metabolic clearance and plasma disappearance rates of human pancreatic tumor growth hormone releasing factor in man.

The metabolic clearance rate (MCR) and plasma disappearance rate (t1/2) of human pancreatic tumor growth hormone releasing factor [hpGRF(1-40)] was determined in normal adult male subjects by single injection and constant infusion techniques. Single injections of 1, 3.3, and 10 micrograms/kg hpGRF(1-40) were administered intravenously, plasma immunoreactive (IR) GRF levels were measured during the subsequent 180 min, and biexponential curve analysis was performed. Graded, dose-constant infusions of hpGRF(1-40) at rates of 1, 3.3, 10, and 33 ng/kg per min were administered and the MCR was calculated from measurement of steady state plasma IR-GRF levels at each infusion rate. The postinfusion disappearance rate was determined by linear regression analysis of plasma IR-GRF levels during the 120-min period after cessation of the infusion. The calculated MCR during the single injection study was 194 +/- 17.5 liters/m2 per d and was not significantly different from the calculated value during the constant infusion study (202 +/- 16 liters/m2 per d). The disappearance rate during the single injection study was subdivided into two linear phases: an initial equilibration phase (7.6 +/- 1.2 min) and a subsequent elimination phase (51.8 +/- 5.4 min). The latter was similar to the linear disappearance rate observed (41.3 +/- 3.0 min) after cessation of the constant infusion. The chromatographic and biologic characteristics of plasma IR-GRF, 30 min after injection, were similar to those of synthetic hpGRF(1-40). The results have been discussed in relation to the MCR of other hypothalamic hormones and have been used to extrapolate secretion rates of GRF in patients with ectopic GRF production.

Adult↗

PubMed1984

Plasma growth hormone responses to constant infusions of human pancreatic growth hormone releasing factor. Intermittent secretion or response attenuation.

Administration of human pancreatic tumor growth hormone (GH) releasing factor (hpGRF[1-40]) as a single injection to normal human subjects stimulates the secretion of GH in a dose-responsive manner. In the present studies, hpGRF(1-40) was infused in a graded stepwise manner over a 6-h period in order to determine whether the GH secretory response would be sustained. Normal adult males received four consecutive 90-min infusions of hpGRF(1-40) at doses of 1, 3.3, 10, and 33 ng/kg per min, preceded and followed by a 90-min saline infusion; and the plasma GH responses were compared with those during a separate control infusion. Plasma GH levels were significantly elevated by each hpGRF(1-40) infusion; and dose responsiveness was evident for the lowest three doses. Mean integrated GH secretory rates for the four doses were 1.95, 3.29, 4.29, and 3.65 times those of the respective control study. Plasma GH responses exhibited considerable variability, frequently decreasing during the latter part of each infusion; and at the highest dose, they decreased continuously beginning shortly after the onset of infusion. Episodic GH secretion occurred in individual subjects during each of the infusion periods. The possible contribution of hypothalamic somatostatin secretion to the diminished GH responsiveness was evaluated by determining plasma thyroid stimulating hormone (TSH) levels during the infusions and the TSH responses to thyrotropin-releasing hormone (500 micrograms i.v.) during a separate hpGRF(1-40) infusion of 2 ng/kg per min. Neither basal nor stimulated TSH levels differed between GRF-infused and control groups. The results indicate that GH secretion is dose responsive to hpGRF(1-40) infusions, though the response to hpGRF(1-40) infusions, though the response is complex. The absence of impaired TSH secretion provides evidence against a mediating role of somatostatin. The explanation for the loss of GH responsiveness remains undetermined but could include GRF-induced receptor down-regulation, a postreceptor effect, or, in spite of our negative results, a somatostatin-mediated inhibition.

Adult↗

PubMed1984

Hemorrhage-induced secretion of corticotropin-releasing factor-like immunoreactivity into the rat hypophysial portal circulation and its inhibition by glucocorticoids.

A paradigm for reliably stimulating ACTH secretion in urethane-anesthetized male rats has been used to examine hypothalamic secretion of corticotropin-releasing factor-like immunoreactivity (CRF-LI) into the hypophysial portal circulation. Hemorrhage of 15% estimated blood volume evoked a maximal 4.6-fold elevation in circulating ACTH levels from an initial level of 178.4 +/- 51.2 (+/-se) to 814.7 +/- 184.6 pg ml-1. The cumulative amount of ACTH secreted in response to hemorrhage was 10-fold greater than the cumulative amount of ACTH secreted by nonhemorrhaged rats (unweighted cumulative effect over all time points). In another experiment from a similarly hemorrhaged group, the hypophysial portal plasma CRF-LI concentration rose 2-fold from an initial level of 429.7 +/- 34.2 to 839.3 +/- 170.4 pg ml-1. Pretreatment with dexamethasone (100 microgram/kg BW, im) had no effect on initial levels of either CRF-LI or ACTH. The hemorrhage-induced elevations of both CRF-LI and ACTH were abolished in dexamethasone-treated rats. The secretory rate of CRF-LI was calculated to be 1.61 +/- 0.7 pg min-1 in nonhemorrhaged animals. Reversible pharmacological hyperpolarization of the paraventricular nuclei by stereotaxically microinjected procaine (15 micrograms/100 nl) reduced portal plasma CRF-LI and peripheral plasma ACTH to undetectable levels. These observations led to the following conclusions: 1) CRF-LI is an important hypothalamic regulator of adenohypophysial ACTH secretion, 2) CRF-LI in the hypophysial portal circulation is derived from CRF-LI-containing neurons within the paraventricular nuclei, and 3) glucocorticoid negative feedback effects can be exerted at the central level.

Adrenocorticotropic Hormone↗

PubMed1984

Human pancreatic growth hormone releasing factor (hpGRF-1-40) stimulates GH release in the ovine fetus.

The effects of growth hormone-releasing factor, hpGRF (1-40), on plasma GH levels were studied in chronically catheterized ovine fetuses between 71 to 134 days of gestation. The basal ovine (o) GH levels in the fetus ranged between 41 - 144 ng/ml, while values in the ewe were often less than 6 ng/ml. hpGRF (1-40), 5 micrograms/kg infused into a fetal vein, markedly stimulated GH release in all nine fetuses. The maximum increase above pretreatment levels (net increases) ranged from 65 ng/ml to 498 ng/ml, with a mean net increase of 229 ng/ml. The responses of oGH in fetuses at younger gestational age appeared to be greater than in older fetuses. Mean plasma oPRL did not change after hpGRF infusion. These results indicate that somatotrophs in fetal sheep in mid- and late gestation have receptors for GRF, and GH secretion may be modulated by GRF at this stage of gestation.

Animals↗

PubMed1984

Influence of corticotropin-releasing factor on reproductive functions in the rat.

The acute administration of 0.015-1.5 nmol ovine corticotropin-releasing factor (CRF) into the lateral ventricle of gonadectomized (or gonadectomized/adrenalectomized) female rats caused a rapid and prolonged dose-related inhibition of LH (but not FSH) secretion. By contrast, the acute peripheral injection of up to 15 nmol CRF was without effect in the same animal preparations. In cycling intact female rats, injection of 1.5 nmol CRF into the brain or of 75 nmol CRF sc inhibited ovulation and blocked the proestrous LH surge in about 50% of the animals. Lower doses of peripherally administered CRF were ineffective. Finally, CRF injected daily sc (15 nmol/day) to female rats during the first 12 days after mating caused a 40% disruption of pregnancy. These results indicate that CRF will lower plasma LH levels and can exert this effect in the absence of circulating steroids of either adrenal or gonadal origin. CRF inhibition of LH secretion, which we have previously reported to be absent in vitro, was unaltered by the opiate receptor antagonist naltrexone or by the ganglionic blocker chlorisondamine. Furthermore, blockade of CRF-induced beta-endorphin or ACTH release into the general circulation by dexamethasone did not interfere with the inhibitory effect of CRF on LH secretion. Such observations suggest that CRF exerts deleterious actions on reproductive functions through brain sites of action which, at least under the experimental mental design used, do not appear to directly involve opiate or peripheral catecholaminergic pathways.

Adrenalectomy↗

PubMed1984

Central nervous system regulation of adrenocorticotropin secretion: role of somatostatins.

Somatostatin-28 (SS-28) and desAA1,2,4,5,12,13[D-Trp8]somatostatin (ODT8-SS), but not somatostatin-14, given intracerebroventricularly, but not when given iv, inhibit stress-induced pituitary ACTH and adrenomedullary epinephrine secretion in rats. The elevation of ACTH after tail-suspension stress is totally prevented by iv administration of antisera raised against corticotropin-releasing factor (CRF). SS-28 and ODT8-SS do not inhibit CRF-induced ACTH secretion in vivo or in vitro. These results are consistent with the hypothesis that SS-28 and ODT8-SS prevent stress-induced ACTH secretion by inhibition of CRF release.

Adrenocorticotropic Hormone↗

PubMed1984

Corticotropin-releasing factor (CRF) acts centrally to inhibit growth hormone secretion in the rat.

The intracerebroventricular administration of 0.15 and 1.5 nmol ovine corticotropin releasing factor ( oCRF ) to freely-moving adult male rats resulted in a dose-related inhibition of spontaneous GH secretion. This inhibition lasted for at least 3 h and was statistically significant at all time points. By contrast, the iv injection of 1.5 nmol oCRF was without effect. These results suggest that CRF can act within the central nervous system to interfere with spontaneous GH secretion.

Animals↗

PubMed1984

Studies of the nature of the interaction between vasopressin and corticotropin-releasing factor on adrenocorticotropin release in the rat.

Arginine-vasopressin (AVP) acts on vasoconstriction and diuresis through two different types of receptors (V1 and V2, respectively). Since AVP also modifies ACTH release, we have attempted to determine which class of receptors mediates the capacity of AVP to increase ACTH secretion and to potentiate the effect of corticotropin-releasing factor (CRF) on the pituitary using two AVP antagonists: [1-deaminopenicillamine-2-(O-methyl)tyrosine]arginine-vasopressin [dPTyr(Me)-AVP], which blocks V1 receptors, and [1-beta-mercapto-beta,beta-cyclopentamethylene propionic acid)2-D-leucine-4-valine]arginine vasopressin [d(CH2)5DLeuValAVP], which interferes with V2 receptors. dPTyr(Me)AVP, but not d(CH2)5DLeuValAVP, inhibited the ACTH-releasing as well as the CRF-potentiating effects of both AVP and its antidiuretic analog [1-deamino-8-D-arginine]vasopressin (dDAVP). These results suggest that the actions of AVP and dDAVP on the corticotrophs is primarily mediated through V1 (pressor-like) receptors.

Adrenocorticotropic Hormone↗

PubMed1984

Central modulation of immunoreactive corticotropin-releasing factor secretion by arginine vasopressin.

Arginine vasopressin (AVP) is regarded as facilitatory to adenohypophysial ACTH secretion at the level of the corticotropic cell. A central facilitatory action of AVP on hypothalamic corticotropin-releasing factor (CRF) has also been postulated, although conclusive evidence on this point is lacking. We directly tested this hypothesis and have found that intracerebroventricular administration of AVP attenuates secretion of immunoreactive CRF (irCRF) into the hypophysial portal circulation in urethane-anesthetized rats. This suppression occurred in a dose-dependent fashion. Conversely, immunoneutralization of AVP or treatment with an AVP antagonist increased portal concentrations of irCRF by 53% and 30%, respectively. These unexpected observations provide evidence for a tonic inhibitory role of central AVP in regulation of irCRF and thus ACTH secretion.

Animals↗

PubMed1984

Synthetic ovine corticotropin-releasing hormone: simultaneous release of proopiolipomelanocortin peptides in man.

The response of plasma proopiolipomelanocortin-derived peptide levels to synthetic ovine corticotropin-releasing hormone (CRH) was studied in six normal men. CRH was given as a 30-sec iv injection of 30 micrograms/kg body weight in the late afternoon, and blood samples were drawn for up to 16 h thereafter. Low levels of immunoreactive (IR)-ACTH, IR-beta-endorphin and IR-lipotropins (LPH) were measured before CRH administration. All subjects had prompt, concomitant, biphasic, and prolonged release of all of these proopiolipomelanocortin-derived peptides. The plasma levels of these IR-peptides rose in all subjects by 5 min after CRH, reached a first peak at 10-15 min, fell until 90 min, rose to a second peak at 2-4 h, and then gradually declined over several hours. The molar concentrations of the IR-peptides closely paralleled one another at all times, especially during the first 90 min after CRH administration. Later, IR-LPH increased slightly more and remained slightly higher than did the other IR-peptides, although the difference was not significant. This observation probably reflects the longer plasma disappearance half-life of IR-LPH. The maximum change (mean +/- SEM) in the concentration of these IR-peptides was similar: IR-ACTH, 18.0 +/- 4.0; IR-LPH, 20.5 +/- 4.0; and IR-beta-endorphin, 16.9 +/- 3.2 fmol/ml. The next morning's circadian rise in IR-peptides was blocked, presumably due to negative feedback inhibition of the hypothalamic-pituitary-adrenal axis by the prolonged high plasma cortisol levels stimulated by CRH the previous evening.

Adrenocorticotropic Hormone↗

PubMed1984

Stimulation of LH fragments with reduced bioactivity following GnRH agonist administration in women.

In eumenorrheic women with endometriosis and in oligo-amenorrheic women with polycystic ovarian disease (PCO), chronic administration of a long-acting GnRH agonist (GnRH-a) reduced the circulating concentrations of estrogens and androgens to levels similar to those of castrated women. The concommittant elevation of LH in both groups suggested that the measured immunoreactive LH had reduced bioactivity. In seven women with endometriosis, bioactive LH (BA LH) measured as the in-vitro secretion of testosterone by dispersed Leydig cells, was significantly (p less than 0.001) reduced from 10.8 +/- 1.2 (SEM) to 4.4 +/- 0.2 mIU/ml at the end of 28 days of GnRH-a therapy. In five women with PCO, BA LH decreased from 44.2 +/- 15.5 to 5.7 +/- 0.6 mIU/ml (p = 0.06). These changes of BA LH appeared to be responsible for the suppression of ovarian androgen secretion during GnRH-a treatment and in turn may have contributed to the profound decreases of estrogen production by reducing the amount of precursor androgen available for aromatization. Free alpha subunit levels increased simultaneously with the decrease of BA LH at the end of therapy, suggesting a post-receptor effect of GnRH-a. Beta subunit levels became undetectable. Cross-reaction of alpha subunit in the RIA for LH was sufficient to only partially account for the LH levels measured. On sephadex G-100 chromatography the excess immunoreactive material was detected at and immediately following the alpha subunit tracer. Further studies will be necessary to elucidate the chemical nature of the immunoreactive LH secreted during GnRH-a therapy.

Endometriosis↗

PubMed1984

Stimulation of growth hormone (GH) and somatomedin C in idiopathic GH-deficient subjects by intermittent pulsatile administration of synthetic human pancreatic tumor GH-releasing factor.

After initial challenges with vehicle alone and then 10 micrograms/kg human pancreatic tumor GH-releasing factor (hpGRF)-40, six adult subjects who had presented in childhood with idiopathic GH deficiency were given 0.33 micrograms/kg hpGRF-40, iv, every 3 h for 5 days. Serum GH levels were monitored daily for 90 min after the 0800 h doses of 0.33 micrograms/kg hpGRF-40, and serum somatomedin C was measured at 0800 and 2000 h. In addition, plasma levels of cholesterol, high density lipoprotein cholesterol, and triglycerides were measured daily at 0800 h. Three hours after the last 0.33 micrograms/kg dose, all subjects were rechallenged with 10 micrograms/kg hpGRF-40. In response to the initial 10 micrograms/kg challenge with hpGRF-40, and although serum GH levels rose in two of six subjects, the mean maximum GH level achieved was no different from that after treatment with vehicle alone. Within 12 h after initiation of the intermittent administration of hpGRF-40, mean +/- SEM serum somatomedin C had risen by 0.1 +/- 0.05 U/ml, and at the end of the 5-day period, had increased from 0.24 +/- 0.07 to 0.78 +/- 0.32 U/ml. In response to the second challenge with 10 micrograms/kg hpGRF-40, serum GH levels rose in three of the four subjects who initially failed to respond or had a less than 1 ng/ml GH response. The increase in serum GH was greater in one of the two subjects who had responded to the first dose. In addition, unlike the first dose, the mean maximal serum GH level achieved in response to the second 10 micrograms/kg dose of hpGRF-40 was higher than that in response to vehicle (P = 0.031). Although there was no statistically significant change during the 5-day period, in plasma cholesterol, high density lipoprotein cholesterol, or triglycerides, the latter exhibited a trend toward increased levels. Our preliminary data show that 5 days of intermittent hpGRF-40 administration augment GH secretion in some adults with GH deficiency, suggesting that somatotropes are present in idiopathic GH deficiency and may be primed by hpGRF-40. The rise in serum somatomedin C to normal levels after multiple injections of hpGRF-40 is encouraging, since circulating levels of somatomedin C may be more important than the increase in immunoreactive GH levels as an index of response for induction of linear growth. The demonstration of biological effects of hpGRF-40 in all six subjects without any serious adverse effects suggests that hpGRF-40 has promise in the treatment of GH deficiency.

Adult↗

PubMed1984

Effects of human pancreatic growth hormone-releasing factor-40 on serum growth hormone, prolactin, luteinizing hormone, follicle-stimulating hormone, and somatomedin-C concentrations in normal women throughout the menstrual cycle.

Human pancreatic tumor GH-releasing factor-40 (hpGRF-40) selectively stimulates GH secretion in normal men and in some adults with GH deficiency. To study its effects in women, we administered hpGRF-40 (3.33 micrograms/kg) or an equivalent volume of vehicle as an iv bolus at 0900 h to 10 normal women during the early follicular, late follicular, and midluteal phases of the menstrual cycle. Serum concentrations of GH, PRL, LH, and FSH were measured at intervals between 0800-1100 h. Serum somatomedin-C concentrations were measured before and 24 h after the administration of vehicle of hpGRF-40. Within 1-3 min after the injection of hpGRF-40 all women described warmth localized to the head and neck and exhibited facial flushing. No changes in pulse rate or blood pressure were noted. When expressed as change from baseline and compared to control values, peak levels of serum GH (nanograms per ml; mean +/- SEM) were higher after hpGRF-40 treatment during the early follicular (5.4 +/- 3.2 vs. 34.9 +/- 8.3; control vs. test day; P = 0.011), late follicular (5.6 +/- 1.5 vs. 25.2 +/- 6.8; P = 0.014), and luteal (0.8 +/- 1.0 vs. 32.7 +/- 12.8; P = 0.033) phases of the menstrual cycle. Similarly, integrated serum GH levels (nanograms per ml/h) were higher after hpGRF-40 administration during the early follicular (0.72 vs. 16.1; P = 0.011), late follicular (0.83 vs. 9.9; P = 0.037), and luteal (-1.54 vs. 17.0; P = 0.036) phases of the cycle. When the increases in serum GH after hpGRF-40 treatment were compared among the phases of the menstrual cycle, however, no differences were found. Serum somatomedin-C values 24 h after hpGRF-40 treatment were higher than those 24 h after vehicle at all stages of the menstrual cycle. hpGRF-40 did not stimulate the release of PRL, LH, or FSH. We conclude that hpGRF-40 stimulates the release of GH, but that in response to the dose used, hpGRF-40-stimulated GH release does not vary during the menstrual cycle.

Adult↗

PubMed1984

Extrahypothalamic growth-hormone-releasing factor (GRF) secretion is a rare cause of acromegaly: plasma GRF levels in 177 acromegalic patients.

To assess the frequency with which acromegaly is caused by ectopic secretion of GRF, we collected plasma samples from 177 unselected acromegalic patients. The samples together with those of three acromegalic patients with previously diagnosed tumors secreting GRF and of normal subjects were assayed in 3 independent GRF RIAs. Plasma immunoreactive GRF (IR-GRF) levels in normal subjects were either undetectable or detectable at levels up to 62.5 pg/ml. In none of the 177 specimens from acromegalic patients were IR-GRF values detectable in all assays, and in the most sensitive assay, the levels were similar to those in normal subjects, with the highest level measuring 82 pg/ml. In contrast, plasma IR-GRF found in the 3 patients with tumors that secreted GRF ranged from 2.0-24.4 ng/ml. These data suggest that extrahypothalamic GRF secretion is a rare cause of acromegaly. However, it is important that this rare cause of acromegaly be diagnosed before the patient has unnecessary surgery and/or irradiation directed at the pituitary. We recommend that plasma IR-GRF be measured in each new acromegalic patient.

Acromegaly↗

PubMed1984

Effect of an LHRH agonist on pituitary and testicular function in rhesus monkeys.

Male rhesus monkeys were given 100 micrograms [(imBzl)-D-His6,Pro9-NEt]-LHRH (LHRH-A), a potent LHRH agonist, s.c. daily for 40 weeks. The first dose of LHRH-A caused acute increases (2-4 h after injection) in serum LH (50-fold), FSH (2 X 5-fold) and testosterone (15-fold) concentrations. Chronic treatment led to a 95% decrease in LH and FSH responses. In spite of a marked decrease in LH response the effect on testosterone response was less evident. Administration of 50 i.u. hCG to control and LHRH-A-treated animals showed that the testicular steroidogenic response was unimpaired by the chronic treatment. Evaluation of the electroejaculated semen at regular intervals showed that there was no consistent reduction in the sperm count of LHRH-A-treated monkeys. Testicular biopsies showed that normal spermatogenesis was occurring in all treated animals, but testicular volume was significantly decreased. These results suggest that, in rhesus monkeys, the pituitary is more susceptible to desensitization by chronic LHRH agonist treatment than are the testes, and that LHRH agonists do not have direct antitesticular effect in rhesus monkeys.

Animals↗

PubMed1984

Pituitary response to growth hormone-releasing factor in diabetes. Failure of glucose-mediated suppression.

To evaluate the mechanism underlying raised growth hormone levels in diabetes, we compared the response to growth hormone-releasing factor (GRF) in type I diabetic and healthy control subjects. In 12 poorly controlled diabetic subjects (fasting plasma glucose 276 +/- 27 mg/dl) basal serum growth hormone levels were elevated by 200-300% (P less than 0.02), yet the incremental increase in growth hormone after GRF injection was no greater than in control subjects. Furthermore, five additional diabetic subjects with normal growth hormone levels after long-term insulin pump treatment also showed an identical response to GRF. Thus, raised basal growth hormone levels in diabetes and the fall that follows intensive insulin treatment may reflect changes in hypothalamic regulation of, rather than in pituitary responsiveness to, GRF. However, when five normal subjects were restudied during glucose infusion, even quite modest hyperglycemia (plasma glucose approximately 150 mg/dl) caused marked suppression of the response to GRF (P less than 0.005). Thus, the "normal" response to GRF in poorly controlled diabetes is actually inappropriate. Failure of the pituitary to suppress in response to hyperglycemia in diabetes implies a second abnormality that may further aggravate disordered growth hormone secretion.

Adolescent↗

PubMed1984

Effects of the (imBzl)D-His6, Des-Gly analog of GnRH on gonadotropin and estradiol secretion in normal women.

The acute gonadotropin and estradiol responses following single subcutaneous injections of 10, 50, 100 and 200 micrograms of [(imBzl)]D-His6,Pro9-NEt]-GnRH were compared to those after 100 micrograms of [D-Trp6, Pro9-NEt]-GnRH. The gonadotropin responses after 50-100 micrograms of the D-His analog of GnRH were equivalent to those following 100 micrograms of the D-Trp analog. The ovarian E2 response, a reflection of the total cumulative secretion of gonadotropins, was similar at 100 micrograms of each analog. The estradiol response paralleled the increasing gonadotropin response accompanying the graded doses of the D-His analog, indicating the lack of a direct inhibitory action of this GnRH agonist on the ovary. Assessment of both gonadotropin and estradiol responses appears to be satisfactory for assessing relative potency among GnRH agonistic analogs.

Adolescent↗