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Biomedical subjects

A D Rogol

Publications and source records attributed to A D Rogol.

At least 199 records · Page 11Linked to original sources
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

Bromocriptine inhibits growth hormone release from rat pituitary cells in primary culture.

The action of the potent dopamine receptor agonist bromocriptine was studied in primary cultures of rat anterior pituitary cells. Bromocriptine inhibited both prolactin and growth hormone release in a concentration-dependent manner. This effect was blocked by the dopamine receptor antagonist spiperone when the agonist and antagonist were added coincidently. In contrast, spiperone was unable to affect the actions of bromocriptine if added 1 min after bromocriptine application or later. These results suggest that dopamine receptors exist not only on mammotrophs, but also on somatotrophs in vitro.

Animals↗
PubMed1984

Camphor toxicity: development of a triage strategy.

Camphor remains in over 950 products listed in Poisindex. To provide triage guidelines for gastric decontamination and referral, we reviewed all camphor ingestions estimated to be 2 mg/kg or greater reported to U. VA (1980-83) and to M.C.V. (1982-83). Seventy-three patients (90%) remained asymptomatic, 3 (4%) developed minor symptoms, and 5 (6%), all ingesting over 59 mg/kg, developed major symptoms. There were no deaths. (table; see text) A literature review of 63 evaluable cases revealed 6 deaths; the mean fatal dose was 199 mg/kg (range 64-570, median 113). Based on these data, we manage asymptomatic patients ingesting camphor at less than 10 mg/kg by observation only 10-30 mg/kg at home with 1 g/kg activated charcoal or emesis, and over 30 mg/kg by gastric decontamination plus referral.

Camphor↗
PubMed1983

Prolactin secretion by human chorion-decidua in vitro: influences of mode of delivery and agents that modify prostaglandin synthesis.

Prolactin production by human decidua was examined with the use of a short-term tissue explant system. Decidua obtained after normal spontaneous vaginal deliveries produced significantly more prolactin than did tissue obtained after elective repeat cesarean section deliveries in the absence of labor (P less than 0.005). Cytosolic prolactin levels did not differ between the two delivery modes. Oxytocin (4.3 X 10(-11) M to 4.3 X 10(-6) M) and eicosatetraenoic acid (10(-7) M to 10(-4) M) had no effect on prolactin production or storage by decidual tissue. Indomethacin at 10(-4) M reduced only levels of stored prolactin but had no effect on stored or produced prolactin at lower concentrations (10(-7) M to 10(-5) M). Arachidonic acid (10(-4) M) suppressed both production and storage of prolactin (P less than 0.05). Decidual tissue from the two delivery modes did not differ in response to the above agents. Although the exact mechanism(s) remains obscure, these results indicate decidual prolactin production is altered by some aspect of labor. The possible involvement of prostaglandin precursors in mediating this production cannot be excluded.

Arachidonic Acids↗
PubMed1983

Effects of human pancreatic tumour growth hormone releasing factor on growth hormone and somatomedin C levels in patients with idiopathic growth hormone deficiency.

Human pancreatic tumour growth hormone releasing factor (hpGRF-40) 10 micrograms/kg was administered intravenously to 6 normal young men and 12 adult patients who had presented in childhood with growth hormone (GH) deficiency (7 patients had isolated GH deficiency, 4 had multiple anterior pituitary hormone deficiencies, and 1 had Hand-Schüller-Christian [HSC] disease). hpGRF-40 administration increased serum GH concentrations in all normal subjects and in 3 of 7 patients with isolated GH deficiency and in the 1 with HSC disease; however, the mean serum GH concentration in the patients who responded was less than that of the normal subjects. Somatomedin C concentrations were increased 24 h after a single dose of hpGRF-40 in 8 of 10 patients with GH deficiency. All subjects experienced flushing in response to hpGRF-40. A patient with isolated GH deficiency received 0.33 micrograms/kg hpGRF-40 every 3 h for 5 days. Despite the modest increase in GH in response to a subsequent dose of 10 micrograms/kg hpGRF-40, serum somatomedin C levels increased within 12 h from 0.06 to 0.1 U/ml and peaked at 0.36 U/ml at 72 h; in addition the patient with HSC disease, treated with hpGRF-40 daily for 5 days, demonstrated an increase in somatomedin C from 0.4 to 0.58 U/ml. The increase after hpGRF-40 in serum GH levels in this patient and the similar or greater responses in 3 of 7 patients suggest that at least some of these patients may have hypothalamic GH-releasing-hormone deficiency. hpGRF-40 may be useful in distinguishing pituitary disease from hypothalamic disease. After hpGRF-40 administration serum somatomedin C levels may increase without a change in serum immunoreactive GH concentrations. Further studies are needed to determine whether hpGRF-40 is useful in promoting linear growth in children with GH deficiency.

Adult↗
PubMed1983

Human pancreatic growth-hormone-releasing factor selectively stimulates growth-hormone secretion in man.

A growth-hormone-releasing factor has been characterised and sequenced from a pancreatic tumour removed from a patient with acromegaly. It is a 40-residue linear peptide. Synthetic human pancreatic growth-hormone-releasing factor (hpGRF-40), 1 microgram/kg bodyweight, was administered as an intravenous bolus to six healthy men. hpGRF-40 selectively stimulated growth-hormone secretion. Serum growth-hormone concentrations were increased within 5 min, reaching a peak between 30 and 60 min (20 . 4 +/- 6 . 5 ng/ml compared with 2 . 1 +/- 0 . 1 ng/ml after placebo). Serum levels of prolactin, thyrotropin, luteinising hormone, and corticotropin (measured indirectly through plasma cortisol) were not increased after administration of hpGRF-40. Similarly, the concentrations of blood glucose, plasma insulin, glucagon, pancreatic polypeptide, cholecystokinin, gastrin, gastric inhibitory peptide, motilin, and somatostatin were unaffected by hpGRF-40. There were no changes in blood pressure, pulse rate, or body temperature, and no side-effects were noted. The characteristics of this peptide fulfil many of the criteria required of the hypophysiotropic growth-hormone-releasing hormone. hpGRF holds promise for a new approach to the diagnosis and treatment of various disorders of growth-hormone secretion.

Acromegaly↗
PubMed1983

The syndrome of anosmia with hypogonadotropic hypogonadism: a genetic study of 18 new families and a review.

Among 18 NIH probands with anosmia and hypogonadotropic hypogonadism (AHH), seven had affected relatives and three had consanguineous parents. Both sexes were equally affected and parents were phenotypically normal. Parental age was not increased. Cleft lip and palate occurred in both eugonadal and hypogonadal persons, a previously reported association that may represent variable expression of AHH. Diabetes mellitus, usually insulin-dependent, was frequent in probands and their families. Other common traits included obesity, cryptorchidism, and hearing loss. All probands were chromosomally normal. The frequency of some dermatoglyphic traits of probands differed from normal, but no trait was unique to AHH. Segregation analysis of our proband sibships was consistent with a hypothesis of autosomal-recessive inheritance with variable expression. However, genetic heterogeneity was apparent when previous reports of familial AHH were surveyed. An X-linked or male sex-limited autosomal-dominant form with unilateral renal agenesis, mental retardation, and hypotelorism has been observed. The infrequent reports of direct male-to-male transmission limit characterization of an autosomal-dominant form of AHH. Our phenotypic analysis suggests that the traits of mental retardation, renal anomalies, hypotelorism, diabetes, and hearing loss may help to distinguish various forms of AHH, whereas cryptorchidism, clefts, and obesity appear in several types of families. At present, genetic counseling is dependent upon establishing inheritance pattern after examination for the known associated anomalies.

Chromosome Banding↗
PubMed1983

Biological activity of a growth hormone-releasing factor secreted by a human tumor.

A substance released by a pancreatic islet cell tumor induced signs and symptoms of acromegaly in a young woman. The culture medium in which the tumor was placed after resection was added to rat anterior pituitary cells and incubated in vitro. Both newly synthesized and total rat growth hormone (GH) release as well as cellular cyclic AMP accumulation were stimulated in a dose-dependent manner by the tumor medium. Coincubation with somatostatin blocked these effects. The increase of cyclic AMP preceded the enhanced GH release, indicating that cyclic AMP may be a second messenger for the tumor factor(s). Neither prolactin nor luteinizing hormone secretion was affected by the tumor medium. When measured by a perfused cell column apparatus, there was a rapid and dramatic release of GH by the dispersed rat pituitary cells during a 2.5-, 10-, and 40-min pulse of tumor medium; both the onset and termination of the GH response reached maximal or control values, respectively, within 5 min. Pretreatment of the tumor medium with pepsin markedly attenuated the tumor medium activity, indicating the peptide nature of the factor(s). Finally, ultrastructural analysis indicated that the somatotrophs were degranulated by the tumor medium, whereas there was no similar effect apparent on the mammotrophs. Whether this tumor polypeptide is identical to native hypothalamic GH-releasing hormone remains to be proved.

Adult↗
PubMed1983

Luteinizing hormone secretion is enhanced by pertussis toxin, cholera toxin, and forskolin. Evidence for the involvement of the cyclic AMP-generating system.

Pertussis toxin, cholera toxin and forskolin, all of which can increase adenylate cyclase activity, stimulated luteinizing hormone LH release from cultured rat anterior pituitary cells. Although cellular cyclic AMP and growth hormone were increased rapidly by cholera toxin and forskolin, enhanced LH release occurred significantly later with no change in total radioimmunoassayable LH (i.e., released plus stored). These data suggest that changes in cyclic AMP levels may regulate the tonic availability of releasable LH in the gonadotroph.

Animals↗
PubMed1983

Endogenous opiates modulate the pulsatile secretion of biologically active luteinizing hormone in man.

We studied the secretion of physiological pools of immunoreactive and biologically active luteinizing hormone in response to endogenous pulses of gonadotropin-releasing hormone (GNRH) in eugonadal men. Concentrations of immunoactive and bioactive luteinizing hormone (LH) were determined in blood drawn at 20-min intervals for 8 h in eight normal men under two conditions: (a) after placebo, in order to evaluate spontaneous LH pulsations in the basal state, and (b) after administration of the opiate-receptor antagonist, naltrexone, which is believed to amplify the pulsatile release of endogenous GNRH. Spontaneous and naltrexone-stimulated secretion of LH occurred in pulses of high biological activity, as measured in the RICT (rat interstitial cell testosterone bioassay), i.e., bioactive:immunoactive LH ratios within both spontaneous and naltrexone-stimulated LH pulses were higher than corresponding interpulse ratios (P less than 0.001). Quantitative characterization of the pulsatile release of bioactive LH revealed the following specific effects of opiate-receptor blockade: increased 8-h mean and integrated serum concentrations of bioactive LH (P less than 0.002), enhanced pulse frequency of bioactive LH release (P less than 0.001), and augmented peak amplitude of bio-LH pulses (P less than 0.01). Moreover, this increase in episodic secretion of bioactive LH was associated with increased 8-h mean and integrated serum testosterone concentrations in these men (P less than 0.05). We conclude the following: (a) LH is normally released in spontaneous pulses of high biological activity in men; (b) when the endogenous GNRH signal is amplified by opiate-receptor blockade, the pituitary gland releases more frequent bioactive LH pulses, which are of high amplitude and contain a high bioactive:immunoactive LH ratio. This increase in pulsatile release of bioactive LH quantitated in the RICT assay in vitro is reflected by acutely increased serum testosterone concentrations in vivo. We infer that modulation of the episodic GNRH signal by endogenous opiates provides another significant mechanism by which the hypothalamus can alter the biological activity of circulating gonadotropic hormone in man. Moreover, observed alterations in the pulsatile pattern of bioactive LH release were associated in turn with significant changes in testosterone concentrations. Thus, we hypothesize that alterations in the properties of the bioactive LH pulse signal can provide an important mechanism for regulating target-cell function within the gonad in states of health or disease.

Adult↗
PubMed1983

Pertussis toxin blocks the somatostatin-induced inhibition of growth hormone release and adenosine 3',5'-monophosphate accumulation.

A protein toxin synthesized by the bacterium Bordetella pertussis has the unique property of blocking a number of receptor-mediated inhibitory systems which are linked to adenylate cyclase. We found that pertussis toxin (PT) eliminates the ability of somatostatin to reduce both basal and GH-releasing factor-stimulated GH release in primary cultures of rat pituitary cells. Furthermore, the ability of somatostatin to reduce GH-releasing factor-induced cAMP accumulation in the cells is significantly attenuated after PT treatment. The PT effect, which is dose dependent and prevented by pretreatment with anti-PT antibodies, represents an alteration in somatostatin efficacy rather than potency. The modification of somatostatin responsiveness persists for at least 5 days after toxin removal. The PT actions on the somatotroph are similar to the effects on other eukaryotic cell types. The combination of available data indicates that the toxin acts on a highly conserved component(s) that is obligatory for transducing the inhibitory hormone message into the cell.

Adenylate Cyclase Toxin↗
PubMed1983

Naloxone attenuates recovery from insulin-induced hypoglycemia in normal man.

The effect of the opioid antagonist, naloxone, on recovery of serum glucose concentrations from insulin-induced (0.1 U/kg) hypoglycemia was determined in five normal adult men. Each subject was studied on 2 separate days, at least 2 weeks apart, during an infusion of either normal saline (6.5 ml/h) or naloxone (0.8 mg/h). The order of the infusions was randomized and double blinded. Although glucose recovery was complete by 120 min after insulin administration during each study, the fractional rate of glucose recovery as determined by analysis of covariance was significantly slower during the naloxone infusions (P = 0.008). Plasma glucagon, serum cortisol, and serum GH concentrations were not different during glucose recovery on either study day. These studies suggest that endogenous opioids contribute to glucose recovery from insulin-induced hypoglycemia and therefore may be important to glucose homeostasis in normal man.

Blood Glucose↗
PubMed1983

Do alpha-adrenergic mechanisms regulate spontaneous or opiate-modulated pulsatile luteinizing hormone secretion in man?

Brain noradrenergic mechanisms participate in the excitatory control of episodic LH release in many experimental animals, including the nonhuman primate. In addition, augmentation of pulsatile LH release in the rodent in response to opiate receptor antagonists is dependent upon intact central noradrenergic pathways. The applicability of these tenets to humans is not known. We tested the excitatory influence of brain noradrenergic systems on pulsatile LH secretion in normal men by administering phenoxybenzamine (an irreversible, preferentially postsynaptic, alpha 1-receptor blocker) or alpha-methyldopa (an inhibitor of brain adrenergic transmission). Five normal men underwent repetitive (every 20 min) venous sampling for 8 h to characterize episodic LH release quantitatively under basal conditions and after the administration of naltrexone, a potent opiate receptor antagonist which stimulates puslatile LH release. Subjects received saline, phenoxybenzamine (1 mg/kg, iv, over 90 min), or alpha-methyldopa (250 mg, orally, every 6 h). The following parameters of spontaneous episodic LH secretion were not altered after phenoxybenzamine or alpha-methyldopa administration: mean and integrated serum LH concentrations, LH pulse frequency, LH pulse amplitude (percentage or milliinternational units per ml increment), and absolute peak serum LH values. In addition, the administration of adrenergic inhibitors did not impede the capacity of naltrexone to significantly augment pulsatile LH secretion in these subjects. We conclude that in the doses used, phenoxybenzamine and alpha-methyldopa do not alter spontaneous or opiate-modulated episodic LH release in normal men.

Adult↗
PubMed1983

Short stature associated with normal growth hormone and decreased somatomedin-C concentrations: response to exogenous growth hormone.

Two prepubertal males with low somatomedin-C concentrations in their sera, but normal growth hormone concentrations, had positive metabolic responses when human growth hormone was administered. An accelerated velocity of growth accompanied the long-term administration of growth hormone. This response was dependent upon the administration of exogenous hormone inasmuch as linear growth was subnormal both before and after administration of growth hormone. The extreme short stature in these individuals may be secondary to a biologically inactive growth hormone molecule that is immunologically reactive or to a decreased dose responsiveness of the cells that produce somatomedin when exposed to the usual concentrations of endogenous growth hormone.

Adolescent↗
PubMed1982

Prolactin binding sites on human chorion-decidua tissue.

An effective procedure has been developed and utilized to demonstrate the presence of prolactin receptors on the plasma membranes of human chorion-decidua cells. Particulate fractions from human chorion-decidua sedimenting between 1,500 and 45,000 x g display optimal binding of 215I-labeled ovine prolactin when incubated at a membrane protein concentration of 200 micrograms per assay tube for 2 hours at 22 degrees C. Specific binding was increased by pretreatment of the membrane particles with 5M magnesium chloride to remove endogenous prolactin. These receptors show binding parameters (affinity, 0.92 x 10(9) L/mode; capacity, approximately 80 fmoles/mg) similar to those of lactogenic receptors in the rabbit mammary gland and, the rabbit and rat liver. The presence of prolactin receptors in human chorion-decidua suggests that may play a role in mediating local action(s) of prolactin such as involvement in the decidualization reaction or in maintaining fetal osmoregulation.

Cell Membrane↗
PubMed1982

Plasma prolactin concentrations and psychopathology in chronic schizophrenia.

Plasma prolactin concentrations in 17 drug-free chronic schizophrenic patients correlated inversely with ratings of their psychopathology. An inverse relationship between psychotic symptoms and plasma prolactin concentrations was particularly clear in patients with normal cerebral ventricular size as determined by computed tomography. The psychosis-prolactin relationship did not hold for schizophrenic patients with large ventricular size. These data suggest that the degree of psychosis is related to dopaminergic activity insofar as this is reflected by plasma prolactin concentrations, especially in schizophrenic patients with normal ventricular size. These findings lend further support to the hypothesis that ventricular size is a meaningful factor in subtyping chronic schizophrenic patients.

Adult↗