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Biomedical subjects

A D Rogol

Publications and source records attributed to A D Rogol.

At least 181 records · Page 10Linked to original sources
PubMed1984

Oxytocin: anti-insulin-like effects in isolated fat cells.

Oxytocin has both insulin-like and insulin antagonistic actions in fat cells in vitro. The anti-insulin-like effects of oxytocin in dispersed rat fat cells have been studied. The magnitude of the anti-insulin-like activity varies with the metabolic pathway of glucose utilization; oxidation [14CO2 production], 32%; glycogen synthesis (D-[U-14C] glucose incorporation into glycogen), 77%. In addition, direct inhibition of the activation of fat cell glycogen synthase has been shown. These inhibitory effects depend upon an intact disulfide ring, since the ability of N-ethylmaleimide-reacted oxytocin to inhibit insulin-stimulated processes was reduced by more than 90% when compared to the intact molecule.

Adipose Tissue↗
PubMed1984

Autoimmunity in congenital rubella syndrome.

Two hundred one deaf adolescents with congenital rubella syndrome and 83 age-matched deaf control subjects were evaluated for the presence of organ-specific antibodies directed against thyroid microsomes, thyroglobulin, pancreatic islets, adrenal cortex, and gastric parietal cells. Positive thyroid microsomal or thyroglobulin antibodies were found in 23.3% (47/201) of the rubella group and in 12.0% (10/83) of control subjects. Nine of 46 (19.6%) in the rubella group and two of nine (22.2%) control subjects with thyroid autoimmunity had thyroid gland dysfunction as indicated by elevated serum TSH concentrations. Neither islet cell nor adrenal cortical antibodies were detected in any subject tested; parietal cell antibodies were detected in 5.5% (8/146) of those in the rubella group and 8.8% (6/68) of control subjects tested, but occurred most frequently in subjects with thyroid autoimmunity (6/36, 16.7% vs 8/178, 4.5%; P less than 0.05). It is recommended that all patients with congenital rubella syndrome be screened for thyroid autoimmunity and that those with positive antibody titers be evaluated for the presence of thyroid dysfunction.

Adolescent↗
PubMed1984

Mesulergine, a new dopamine agonist: effects on anterior pituitary function and kinetics.

We investigated the effects of single doses of mesulergine on basal and thyrotropin-releasing hormone (TRH)-stimulated serum levels of several anterior pituitary hormones in healthy men and defined its kinetics. We also compared the effects on serum prolactin (PRL) levels of three doses (0.1, 0.35, and 0.5 mg) of mesulergine to those in response to 2.5 mg bromocriptine. Secretory rates of PRL before the first dose of TRH were not affected by any dose of mesulergine or bromocriptine. TRH-stimulated PRL secretion was not altered by 0.1 mg mesulergine but was blunted by both the 0.35- and 0.5-mg doses at 10 A.M. and 1 P.M. Bromocriptine inhibited TRH-stimulated PRL secretion at 10 A.M. and 8 P.M. When analyzed as the 8 A.M. to 8 P.M. and the 8 P.M. to 9 A.M. (day 2) intervals, PRL secretion was not changed by 0.1 or 0.35 mg mesulergine but was suppressed during both periods by the 0.5-mg dose. A dose-response relationship was evident, however, between mesulergine and PRL secretion during both the 8 A.M. to 8 P.M. (R2 = 0.27) and the 8 P.M. to 9 A.M. (day 2; R2 = 0.18) intervals. Bromocriptine lowered PRL secretion during both intervals. Secretory rates of growth hormone during these intervals were not affected by 0.1 mg or 0.35 mg mesulergine but were increased during both intervals by the 0.5-mg dose. Neither the secretory rates of thyrotropin in response to TRH nor those of cortisol, luteinizing hormone, or follicle-stimulating hormone were changed by 0.1 or 0.35 mg mesulergine.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1984

The effect of exogenous growth hormone on insulin requirements during closed loop insulin delivery in insulin-dependent diabetes mellitus.

The amount of insulin required to maintain similar blood glucose concentrations during an eight hour infusion of either saline or growth hormone (2 micrograms/kg/hr) was determined in five fed, insulin-dependent diabetic subjects during closed-loop insulin delivery. Elevations of serum growth hormone concentrations to levels previously observed in poorly controlled diabetic subjects were not accompanied by differences in the amount of insulin required to maintain blood glucose concentrations at levels comparable to those observed during the saline infusion. Specifically, no early insulin-like nor late anti-insulin effects of physiologic increases in serum growth hormone concentrations (10.27 +/- 0.23 mg/ml vs 5.69 +/- 1.5 mg/ml, P less than 0.05) on mean hourly blood glucose levels or mean hourly insulin requirements were observed. These studies suggest that serum growth hormone concentrations similar to those observed in poorly controlled diabetics do not affect the insulin requirements of well-insulinized diabetic subjects.

Adolescent↗
PubMed1984

Sex differences in the cyclic adenosine 3':5'-monophosphate and growth hormone response to growth hormone-releasing factor in vitro.

Human pancreas tumor growth hormone-releasing factor (hpGRF) induced more cellular cyclic adenosine 3':5'-monophosphate (AMP) accumulation and growth hormone release from male than female rat anterior pituitaries in vitro. This was reflected in a change in maximal levels achieved (efficacy) rather than potency, and was not an exclusive effect of hpGRF peptide; prostaglandin E2 also exhibited these effects. These data suggest that the origin of the larger spontaneous peak growth hormone levels in male rats may be within the anterior pituitary gland.

Animals↗
PubMed1984

Performance of LH pulse-detection algorithms at rapid rates of venous sampling in humans.

To assess the influence of the sampling rate on the quantitative characterization of pulsatile luteinizing hormone (LH) release, we withdrew blood at 4-min intervals for 8 h in five men and at 1-min intervals for 2 h in six other men. For comparative purposes, significant LH pulses were enumerated by three independent, computerized pulse-detection algorithms currently available. Our results indicate that, although the absolute number of LH pulses detected was influenced by the particular algorithm used and the estimate of intra-assay variance, all three analyses yielded increased pulse-frequency estimates at more intensive rates of venous sampling. Moreover, using a fourth, modified pulse-detection algorithm intended to maximize recognition of true-positive LH pulses while minimizing both false-positive and false-negative pulses, we observed that venous sampling at 4- and 1-min intervals exposed 4- and 12-fold more LH pulses, respectively, than could be discerned at conventional sampling rates. At rapid rates of venous sampling, the pattern of LH pulses comprised high-frequency, low-amplitude LH pulsations superimposed on lower-frequency LH peaks. This pattern suggests that the pituitary gland is responsive to high rates of intermittent neural stimulation. Moreover, these observed profiles are consistent with rapid initial rates of LH disappearance and/or distribution that we could demonstrate after intravenous bolus injections of purified LH in hypogonadotropic volunteers. In conclusion, we have compared results from three different pulse-detection algorithms at various rates of venous sampling and demonstrated a critical influence of sampling rate on apparent LH pulse frequency in humans.

Adult↗
PubMed1984

Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man.

We have tested the participation of endogenous opiate pathways in the negative feedback actions of gonadal steroids on pulsatile properties of luteinizing (LH) hormone release in normal men. To this end, sex steroid hormones were infused intravenously at dosages that under steady state conditions selectively suppressed either the frequency or the amplitude of the pulsatile LH signal. The properties of pulsatile LH secretion were assessed quantitatively by computerized analysis of LH series derived from serial blood sampling over 12 h of observation. When the pure (nonaromatizable) androgen, 5-alpha-dihydrotestosterone, was infused continuously for 108 h at the blood production rate of testosterone, we were able to achieve selective inhibition of LH pulse frequency akin to that observed in experimental animals after low-dosage androgen replacement. Under these conditions, serum concentrations of testosterone and estradiol-17 beta did not change significantly, but serum 5 alpha-dihydrotestosterone concentrations increased approximately two- to threefold, with a corresponding increase in levels of its major metabolite, 5 alpha-androstan-3 alpha, 17 beta-diol. In separate experiments, the infusion of estradiol-17 beta at its blood production rate over a 4.5-d interval selectively suppressed LH pulse amplitude without influencing LH pulse frequency. Estrogen infusion increased serum estradiol-17 beta levels approximately twofold without significantly altering blood androgen concentrations. We then used these schedules of selective androgen or estrogen infusion to investigate the participation of endogenous opiates in the individual inhibitory feedback actions of pure androgen or estrogen on pulsatile LH release by administering a potent and specific opiate-receptor antagonist, naltrexone, during the infusions. Our observations indicate that, despite the continuous infusion of a dosage of 5 alpha-dihydrotestosterone that significantly suppresses LH pulse frequency, co-administration of an opiate-receptor antagonist effectively reinstates LH pulse frequency to control levels. Moreover, during the infusion of a suppressive dose of estradiol-17 beta, opiate receptor blockade significantly augments LH pulse frequency and increases LH peak amplitude to control levels. Thus, the present studies in normal men demonstrate for the first time that the selective inhibitory action of a pure androgen on LH pulse frequency is effectively antagonized by opiate-receptor blockade. This pivotal observation indicates that opiatergic and androgen-dependent mechanisms specifically and coordinately control the hypothalamic pulse generator for gonadotropin-releasing hormone (GnRH)

Adult↗
PubMed1984

Generalized convulsions as the presenting sign of amoxapine intoxication.

Two infants presented for medical evaluation with sudden onset of seizures or coma, without obvious cause. Suspicious circumstances led to toxicological screening analysis. Amoxapine, a recently released antidepressant, was found in the gastric contents of both children an undetermined time after the putative ingestion, but elevated serum concentrations were noted only in one. The pharmacokinetics are described. There were no obvious cardiotoxic or anticholinergic effects in these infants. Thus, they, like older children and adults, manifest mainly central nervous system toxicity rather than the cardiotoxicity and anticholinergic effects of overdose seen with tricyclic antidepressants.

Amoxapine↗
PubMed1984

Human pancreatic tumor growth hormone (GH) - releasing factor and cyclic adenosine 3',5'- monophosphate evoke GH release from anterior pituitary cells: the effects of pertussis toxin, cholera toxin, forskolin, and cycloheximide.

Both synthetic human pancreatic tumor GH-releasing factor (hpGRF) and prostaglandin E2 (PGE2) rapidly stimulate cellular cAMP accumulation in and GH release from primary cultures of rat anterior pituitary cells. SRIF inhibits both of these actins. A 1-h treatment with the protein synthesis inhibitor cycloheximide potentiates hpGRF-induced cAMP accumulation for hours and GH release for the first hour. This indicates that a rapidly turning over protein tonically mutes the degree of hpGRF-stimulated cAMP accumulation. Pretreatment of the cells with pertussis toxin amplifies hpGRF- and PGE2-stimulated cAMP levels and GH release; pertussis toxin also attenuates the ability of SRIF to affect these variables. This suggests that an inhibitory coupling protein contributes to these events. Finally, cholera toxin and forskolin are also potent stimulators of cAMP accumulation and GH release. We conclude that hpGRF-evoked GH release and the inhibitory action of SRIF are closely correlated with the cAMP-generating system.

Animals↗
PubMed1984

Effect of testosterone on somatomedin-C concentrations in prepubertal boys.

To investigate the role of testosterone (T) in the pubertal elevation of somatomedin-C (SmC), six prepubertal GH-deficient boys were each given 7-day courses of GH alone (0.05 U/kg X day, im), T alone (T propionate; 25 mg/day, im), and a combination of GH and T at the same dosages. Plasma SmC levels were determined on samples drawn at the start and finish of each period, and each course was separated by a 7-day period. SmC was also measured before and after a course of T propionate (25 mg/day, im) in four GH-sufficient boys with delayed adolescence. In the GH-deficient boys, GH and the combination of GH and T resulted in comparable and significant increments of SmC (mean change, 0.68 U/ml after GH and 0.63 U/ml after the combination of GH and T). T alone caused no change in SmC in the GH-deficient boys (mean change, 0.09 U/ml), but resulted in increases in all four GH-sufficient subjects (mean change, 1.29 U/ml). In a single subject with constitutionally delayed puberty, the integrated 24-h GH concentration rose from 2.8 ng/ml before to 5.8 ng/ml after T therapy. Both the number and amplitude of GH secretory events were greater after therapy. These data show that T stimulates SmC production in prepubertal boys who can secrete GH, but not in those who are GH deficient. We postulate that the effect of T in this regard is due to its effect on pituitary GH secretion. Although the T levels were within the pharmacological range, physiological levels of T (e.g. at puberty) may be responsible for the adolescent SmC increment in men.

Adolescent↗
PubMed1984

Human pancreatic tumor growth hormone-releasing factor: dose-response relationships in normal man.

Human pancreatic GRF (hpGRF-40; 1 microgram/kg, iv) selectively stimulates GH release in normal men (9). We now report the effects of graded doses of hpGRF-40 on GH release in 12 normal men. Mean peak increments in serum GH after vehicle and the various doses of hpGRF-40 were 1.13, 11.40, 14.60, 17.01, 14.45, and 15.60 ng/ml after vehicle and 0.1, 0.33, 1.0, 3.3, and 10 micrograms/kg hpGRF-40 (iv bolus), respectively. Peak values were observed 30-60 min after hpGRF-40 treatment. There was considerable variability of responsiveness among individual subjects, and no dose-response relationship between the doses and maximal GH values was found. However, the higher doses of 3.3 and 10.0 micrograms/kg resulted in a more prolonged and biphasic pattern of GH release. A side effect of facial flushing of less than 5-min duration occurred in 4 or 6 subjects who received 3.3 micrograms/kg and in all 5 who received 10 micrograms/kg of hpGRF-40. No changes in serum glucose, LH, TSH, PRL, plasma cortisol, or 8 enteropancreatic hormones occurred after hpGRF-40 treatment. There were small increases in serum somatomedin C levels 24 h after the administration of various doses of hpGRF-40 in 11 of 13 studies. Plasma immunoreactive GRF levels measured 5 min after injection were 0.09, 2.0, 4.9, 23.9, and 66.6 ng/ml after 0.1, 0.33, 1.0, 3.3, and 10 micrograms/kg hpGRF-40, respectively. Serum GH responses after insulin-induced hypoglycemia were compared to GH responses after hpGRF-40. Comparable peak GH stimulation occurred with both provocative tests. Mean +/- SEM peak GH was 20.2 +/- 1.0 ng/ml after insulin and 20.9 +/- 3.2 after hpGRF-40 treatment. hpGRF-40 selectively stimulates GH release in normal men over a dose range of 0.1-10 micrograms/kg and is an effective probe to investigate the dynamics of GH release.

Adult↗
PubMed1984

Follicle-stimulating hormone-secreting pituitary tumor with concomitant elevation of serum alpha-subunit levels.

Hypersecretion of FSH and alpha-subunit was documented in a man with a pituitary adenoma that was previously diagnosed on clinical grounds as nonfunctioning who had been treated by transsphenoidal surgery and postoperative irradiation. Postoperatively, the patient had high serum FSH levels and normal serum, LH levels. Ten years after the surgery, immunostaining of the tumor revealed the presence of beta FSH, beta LH, and beta TSH in the cytoplasm of scattered adenoma cells, although not always in the same cells. LH levels were elevated during the middle portion of the 12 yr that this patient was followed. However, as LH immunoreactivity was shown (in specimens recently drawn) to be largely due to cross-reactivity in the alpha-subunit RIA, the high LH values may represent high alpha-subunit levels. The elevated FSH levels and alpha-subunit concentrations did not rise after GnRH administration. Thus, during the course of 12 yr, this patient's tumor hypersecreted FSH and alpha-subunit and possibly LH. The evolution of these events may represent the natural history of the tumor or the effects of the therapeutic modalities used. We conclude that adult men with pituitary tumors and complaints of hypogonadism should be evaluated for a FSH-secreting tumor.

Adenoma↗
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

Divergent influences of calcium ions on releasing factor-stimulated anterior pituitary hormone secretion in normal man.

To investigate the influence of calcium ions on the secretion of anterior pituitary hormones in response to stimulation by exogenous hypothalmic releasing factors in man, we measured serum concentrations of pituitary hormones serially during a continuous infusion of combined TRH (2 micrograms/min) and GnRH (1 microgram/min), with concomitant iv saline or calcium administration. Compared to saline, calcium administration was associated with a significant increase in GnRH-TRH-stimulated LH and FSH release and a corresponding rise in serum testosterone concentrations. The effect of calcium ions on gonadotropin secretion was specific, because releasing factor-stimulated secretion of TSH and PRL was suppressed by hypercalcemia. Serum concentrations of GH were not significantly altered under these conditions. In summary, the present results provide the first in vivo evidence that acute infusion of calcium ions augments GnRH-TRH-stimulated secretion of LH and FSH, with an accompanying increase in serum testosterone levels. In contrast, hypercalcemia did not alter serum GH concentrations, and it suppressed GnRH-TRH-stimulated release of PRL and TSH. We conclude that calcium ions can selectively influence releasing factor-stimulated secretion of certain anterior pituitary hormones in man.

Adult↗
PubMed1984

Intensified rates of venous sampling unmask the presence of spontaneous, high-frequency pulsations of luteinizing hormone in man.

To test the validity of venous sampling rates that are generally used to characterize pulsatile LH release in man (e.g. sampling every 15-20 min), we characterized apparent LH pulse frequency in blood withdrawn variously at 20- or 4-min intervals in 19 men, at 2-min intervals in 14 men, and at 1-min intervals in 6 men. In an effort to minimize detection bias, significant LH pulses were evaluated objectively using a computerized pulse-detection algorithm, which tended to maximize recognition of true-positive LH pulses, and minimize false-positive and false-negative pulses. Under these conditions, intensified rates of venous sampling at 4-, 2-, and 1-min intervals exposed approximately 3.6, 4.9, and 13.7-fold more LH pulses, respectively, than could be discerned at a 20-min sampling frequency. In addition, more rapid rates of venous sampling disclosed a previously unobserved pattern of LH pulses, in which higher frequency, lower amplitude LH pulsations were interposed among low frequency, high amplitude LH peaks. Quantitatively, LH pulses unmasked by intensified rates of venous sampling exhibited significantly lower pulse amplitudes, expressed either as a fractional (%) or absolute (mIU/ml) increment, than pulses identified at 20-min intervals. In conclusion, we demonstrated that intensified rates of venous sampling unmask a significant number of otherwise unrecognized LH pulses in the circulation of normal men. Moreover, because generally employed sampling rates overlooked these more rapid physiological fluctuations in LH concentrations, patterns of both high and low frequency LH pulsations must now be characterized in various states of health and disease using more rapid sampling paradigms.

Adult↗
PubMed1984

Growth hormone release in response to human pancreatic tumor growth hormone-releasing hormone-40 in children with short stature.

Forty children with short stature were evaluated for GH reserve after pharmacological tests and after a single iv injection of human pancreatic tumor GH-releasing hormone [hpGRH-40). These children were grouped into four diagnostic categories: 1) idiopathic GH deficiency (n = 10); 2) organic hypopituitarism (n = 7); 3) intrauterine growth retardation (n = 5); and 4) constitutional delay of growth and/or familial short stature (n = 18), by standard clinical criteria and physiological and pharmacological tests of GH reserve. Venous blood was sampled for GH concentrations on 2 consecutive days: on day 1, after the iv administration of L-arginine (0.5 g/kg for 30 min) and oral administration of L-dopa (9 mg/kg), and on day 2, after the administration of hpGRH-40, 3.3 micrograms/kg, as an iv bolus. No GH-deficient patient in categories 1 or 2 increased his/her circulating GH concentration to more than 7 ng/ml after the arginine-L-dopa test; however, six children had marked GH responses after hpGRH-40 administration. As a group the lowest peak responses (mean +/- SE) to GRH were found in the organic hypopituitary (3.4 +/- 1.1 ng/ml) and in the idiopathic GH deficiency (8.2 +/- 2.4 ng/ml) categories. All children in the intrauterine growth retardation and constitutional delay of growth (controls for the GH-deficient children) responded briskly to hpGRH-40, although there was wide variation of the peak GH levels (5-51 ng/ml). Circulating concentrations of somatomedin-C did not differ in subjects in any category 24 h after hpGRH-40 injection when compared to basal values. These data indicate that hpGRH-40 can be employed to evaluate GH reseve in short children and may be useful in the diagnosis of hypothalamic-pituitary disorders.

Adolescent↗