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Biomedical subjects

A D Rogol

Publications and source records attributed to A D Rogol.

At least 127 records · Page 7Linked to original sources
PubMed1989

Changes in growth hormone (GH) secretion and in growth during puberty.

During normal adolescent development in males testosterone induces the adolescent growth spurt, at least in part, by increasing GH production via an increase in the amplitude of the peaks of GH which are released, and not by increasing the frequency of GH pulses. Testosterone and estrogen administration at low or modest doses to individuals with the capacity to produce GH causes GH production and IGF-I levels to increase. Testosterone given to GHD patients does not increase either of these factors. In addition, there may be two actions for growth promotion by testosterone. One unequivocally results from an increase in GH production in the presence of low or modest levels of testosterone. A direct action on bone growth is probably present also, as reflected by the growth promoting effect of oxandrolone, a weak androgen, in boys with CDGA in the absence of increased GH production.

Adolescent↗
PubMed1988

Pertussis toxin treatment attenuates some effects of insulin in BC3H-1 murine myocytes.

The effects of pertussis toxin (PT) treatment on insulin-stimulated myristoyl-diacylglycerol (DAG) generation, hexose transport, and thymidine incorporation were studied in differentiated BC3H-1 myocytes. Insulin treatment caused a biphasic increase in myristoyl-DAG production which was abolished in myocytes treated with PT. There was no effect of PT treatment on basal (nonstimulated) myristoyl-DAG production. Insulin-stimulated hydrolysis of a membrane phosphatidylinositol glycan was blocked by PT treatment. ADP-ribosylation of BC3H-1 plasma membranes with [32P]NAD revealed a 40-kDa protein as the major PT substrate in vivo and in vitro. The time course and dose dependence of the effects of PT on diacylglycerol generation correlated with the in vivo ADP-ribosylation of the 40-kDa substrate. Pertussis toxin treatment resulted in a 71% attenuation of insulin-stimulated hexose uptake without effect on either basal or phorbol ester-stimulated uptake. The stimulatory effects of insulin and fetal calf serum on [3H]thymidine incorporation into quiescent myocytes were attenuated by 61 and 59%, respectively, when PT was added coincidently with the growth factors. Nonstimulated and EGF-stimulated [3H]thymidine incorporation was unaffected by PT treatment. These data suggest that a PT-sensitive G protein is involved in the cellular signaling mechanisms of insulin.

Adenosine Diphosphate Ribose↗
PubMed1988

Neuroendocrine function in survivors of childhood acute lymphocytic leukemia and non-Hodgkins lymphoma: a study of pulsatile growth hormone and gonadotropin secretions.

To assess the neuroendocrine function of long-term survivors of childhood hematologic malignancies, 10 patients who had acute lymphocytic leukemia and two who had non-Hodgkins lymphoma (NHL) (mean age 13.5 +/- 1 year) were studied, who were treated with similar chemotherapeutic regimens with or without 2,400 rads of prophylactic cranial irradiation. Pharmacologic growth hormone (GH) stimulation tests and three graded doses of the GH-releasing hormone (1-40-OH-GRH, 0.1, 0.3, and 1 microgram/kg) were administered. Venous sampling for GH and gonadotropin determinations was done at 20-min intervals for 24 h, and a new computerized pulse detection algorithm was used to analyze pulses. All the patients who had neuroendocrine abnormalities were in the cranially irradiated group. Two of the 12 patients were GH deficient, and had abnormal 24-h secretory profiles, blunted GH responses to pharmacologic stimuli, and minimal responses to the three doses of GRH. The pulsatile properties of luteinizing hormone (LH) were normal in 10 of the 12 nongonadally irradiated patients, irrespective of previous cranial irradiation and pubertal stage, when compared with available normative data.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Atenolol enhances growth hormone release to exogenous growth hormone-releasing hormone but fails to alter spontaneous nocturnal growth hormone secretion in boys with constitutional delay of growth.

We tested the hypothesis that selective beta 1-adrenergic blockade will enhance growth hormone (GH) secretion in boys with constitutional delay of growth in response to both exogenously administered growth hormone-releasing hormone as well as to endogenous GH-releasing hormone pulsations. The study group comprised eight healthy, short, prepubertal boys ranging from 7 2/12 to 15 0/12 yr old with bone ages delayed 15 to 42 months. All had demonstrated GH levels of greater than 10 ng/ml following a pharmacologic or physiologic stimulus. During two consecutive nights, blood samples were withdrawn every 20 min for GH determination between 2000 and 0800 h. Immediately after each 0800 h blood withdrawal, 1 microgram/kg of GH-releasing hormone (1-40)-OH was administered intravenously to each subject and blood was withdrawn every 15 min for an additional 2 h. During the day before the second overnight sampling period each subject received atenolol, 25 mg orally, at 1030 and 1600 h to induce beta-adrenergic blockage. The six subjects in whom beta-adrenergic blockade could be documented had enhanced GH release after GH-releasing hormone administration on the atenolol treatment day both in terms of higher peak GH levels achieved (p less than 0.05) as well as greater total GH secretion (3916 +/- 701 versus 5624 +/- 986 ng/ml.min, p less than 0.01). In contrast, there were no differences in endogenous, unstimulated nocturnal GH pulse characteristics between study and control days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Acceleration of growth rate in growth hormone-deficient children treated with human growth hormone-releasing hormone.

Twenty-four growth hormone-deficient children were treated with growth hormone releasing hormone-40 (GHRH) for 6 months or longer. GHRH (1 to 4 micrograms/kg of body weight per dose) was administered subcutaneously every 3 h (n = 10); or every 3 h overnight only (n = 10); or by twice daily injections (n = 4). Twenty-one children had an increase in growth rate during GHRH treatment. The growth velocities (mean +/- SD; cm/yr) before and during treatment were, respectively: every 3 h 3.5 +/- 1.4 versus 10.0 +/- 2.2, p = 0.0001; overnight only 3.4 +/- 1.0 versus 6.2 +/- 2.1, p = 0.008; twice daily injections 3.2 +/- 1.8 versus 7.9 +/- 2.4, p = 0.06. Using these three modes of GHRH administration, different total daily amounts of GHRH were administered. Regression analysis of average daily dose versus growth velocity revealed a correlation coefficient (r) value of 0.57, p = 0.004. Sixteen children received extended treatment for periods varying from 9 to 30 months. Of these, seven children were treated continuously for 9 months with pump overnight only and 5 for 12 months with pump every 3 h. Their growth velocities were sustained at a similar rate as those observed at 6 months. Six children received both twice daily and three hourly treatments consecutively. The growth velocities were similar during both treatments. Eleven children developed circulating antibodies to GHRH during treatment, however, all 11 had accelerated growth rates during GHRH therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Physiological profiles of episodic progesterone release during the midluteal phase of the human menstrual cycle: analysis of circadian and ultradian rhythms, discrete pulse properties, and correlations with simultaneous luteinizing hormone release.

To define the physiological relationships between episodic progesterone and LH release, we measured serum progesterone and LH concentrations in blood sampled at 10-min intervals for 24 h in seven young women in the midluteal phase of the menstrual cycle. The resultant time series were assessed further by Fourier transformation, Cluster analysis, and cross-correlation analysis with autoregressive modeling. These techniques permitted an examination of circadian rhythms, discrete (ultradian) pulse properties, and simultaneous or lagged correlations between progesterone and LH release. We found the following. 1) Both serum LH and progesterone concentrations had significant circadian periodicities, with similar acrophases (times of maximal nyctohemeral values). LH and progesterone also manifested multiple ultradian rhythms of similar periodicities (range, 48-241 min). 2) Discrete serum progesterone peaks occurred at a mean interpulse interval of 118 +/- 12 (+/- SE) min, had durations of 92 +/- 12 min, and had incremental amplitudes of 4.3 +/- 0.9 ng/mL (14 +/- 3 nmol/L). The frequency and duration characteristics of the progesterone and LH peaks were not significantly different, but progesterone fractional peak amplitudes were one quarter those of LH pulses. 3) Fractional progesterone peak amplitudes in the seven women correlated inversely (r = -0.811) with 24-h mean LH concentrations, suggesting a negative feedback relationship between progesterone and LH release. 4) LH and progesterone interpulse intervals both exhibited significant nyctohemeral variations, with diurnal amplitudes of 73 +/- 12 min for LH and 43 +/- 8.9 min for progesterone (P less than 0.01). 5) Significant positive cross-correlations existed in all seven women between serum LH and progesterone concentrations considered simultaneously and at progesterone time lags of 10-50 min. By autoregressive modeling, the later (20-50 min) cross-correlations could be accounted for by sustained autocorrelations in the individual progesterone and LH time series and significant cross-correlations between LH and simultaneous progesterone concentrations and between LH and 10-min lagged progesterone concentrations. We conclude that progesterone release occurs in a periodic (circadian and ultradian) fashion as well as in a discrete (episodic or pulsatile) mode. Moreover, both positive and negative feedback relationships operate to coordinate LH and progesterone secretion in the midluteal phase of the human menstrual cycle.

Adult↗
PubMed1988

A persistent pattern of varying pituitary responsivity to exogenous growth hormone (GH)-releasing hormone in GH-deficient children: evidence supporting periodic somatostatin secretion.

The pattern and degree of variation in pituitary responsivity to GHRH was examined in four GH-deficient children (two boys and two girls, aged 4 3/12 to 10 4/12 yr). All children were studied before and on multiple (three to six per child) occasions during long term GHRH therapy (1 or 2 micrograms/kg, sc, every 3 h) in an identical fashion. Each study comprised withdrawal of blood for serum GH measurements every 20 min between 2000 and 0800 h. All subjects received GHRH at 2000, 2300, 0200, and 0500 h as well as at 0800, 1100, 1400, and 1700 h throughout the long term treatment period (6-18 months). Although all children had low level (less than 7.0 micrograms/L) pulsatile GH secretion during baseline studies, the maximal peak values occurred at times other than 0500 h. Before GHRH treatment, serum GH levels rose significantly in response to 91% (62 of 68) of the GHRH doses administered. GH pulse amplitudes varied throughout the studies in all children, and this variability persisted despite 1300-3600 consecutive doses in each child. In all 17 study periods the highest serum GH concentration occurred shortly after the 0500 h GHRH dose. The mean peak GH concentration after the 0500 h GHRH dose [18.4 +/- 3.5 (+/- SE) micrograms/L] was significantly higher than those after the 2000 h (5.3 +/- 1.0 micrograms/L; P = 0.0001), 2300 h (7.4 +/- 2.1 micrograms/L; P = 0.0003), and 0200 h (10.9 +/- 2.5 micrograms/L; P = 0.011) doses. These results demonstrate that the responsivity of the pituitary to GHRH varies throughout the night in some GH-deficient children. There appears to be a direct relationship between the time of night and the degree of pituitary responsivity to GHRH. We suggest that this variable responsivity may be due to intermittent hypothalamic somatostatin secretion.

Child↗
PubMed1988

Acute androgen receptor blockade increases luteinizing hormone secretory activity in men.

To investigate the nature of androgen feedback mechanisms in normal men, we studied the hypothalamo-pituitary responses to administration of a potent, highly selective nonsteroidal androgen receptor antagonist, flutamide HCl (1 g/day, orally, for 3 days). The impact of reversible blockade of endogenous androgen action was assessed in 11 normal men by analyzing quantitative alterations in specific pulsatile properties of LH secretion basally (hypothalamic regulation) and after 2 (n = 6) consecutive iv pulses of exogenous GnRH (pituitary responsiveness). Androgen blockade resulted in significant increases in 1) 12-h mean and integrated serum immunoactive LH concentrations (P = 0.01), 2) LH pulse frequency (P = 0.01), and 3) mean interpulse (valley) serum LH concentrations (P = 0.02) and maximal LH peak heights (P = 0.01). Additionally, there were significant decreases in LH interpulse interval (P = 0.02), LH peak duration (P = 0.02), and interpeak valley duration (P = 0.02). The augmented LH pulsatility reflected enhanced hypothalamic activity, since 1) pituitary secretory responses to exogenous GnRH pulses were not altered, and 2) multiple parameter deconvolution disclosed an increased number of computer-resolved LH secretory bursts generated per 12 h, with no changes in the apparent half-duration of LH secretory impulses or the calculated mass of LH released per secretory burst. We conclude that endogenous androgens act selectively to modulate the number of spontaneous LH secretory bursts in man.

Adult↗
PubMed1987

Actions of calcium ions and a calcium-influx blocker on basal and TRH- and GnRH-stimulated hormone release in patients with pituitary adenomas.

We investigated the influence of calcium ions on the secretion of anterior pituitary hormones basally and in response to exogenous hypothalamic releasing factors in 6 men with pituitary tumors. To this end, concentrations of LH, FSH, TSH, growth hormone and prolactin were measured in blood collected at 10-min intervals basally and during a continuous infusion of combined TRH (2 micrograms/min) and GnRH (1 microgram/min). Study sessions were randomized to iv saline, calcium, or diltiazem infusions or oral diltiazem administration. Our results indicate that in contrast to responses in normal men, iv calcium injections do not suppress circulating prolactin concentrations in patients with prolactin-secreting pituitary tumors. Moreover, neither oral diltiazem administration for one week nor acute iv diltiazem infusion suppressed the hyperprolactinemia of tumor patients. However, there were significant effects of drug and calcium treatments on serum concentrations of FSH, GH and testosterone, but not LH or TSH. Moreover, during GnRH-TRH stimulation, there were significant differences in LH, TSH, and testosterone responses in tumor patients compared to normal men. In summary, iv calcium infusion was associated with invariant basal release of anterior pituitary tumoral hormones in patients with pituitary adenomas. However, there were significant differences in the GnRH/TRH-stimulated release of certain anterior pituitary hormones in tumor patients compared to normal men in response to iv calcium and the calcium-channel antagonist, diltiazem.

Adenoma↗
PubMed1987

Selective beta 1-adrenergic receptor-blockade with atenolol enhances growth hormone releasing hormone and mediated growth hormone release in man.

The growth hormone (GH) responses to a single bolus injection of the growth hormone releasing hormone (GRH) were examined in the basal state and in the presence of beta-adrenergic receptor blocking agents of different specificity in ten normal men. During a constant five-hour infusion of 56 micrograms/min of propranolol (nonselective beta-adrenergic receptor-blocker) in seven subjects studied, there was a significant augmentation of the GH release in response to exogenous GRH compared to the GH response during saline infusion, as measured by the peak serum GH concentrations after GRH (P = 0.019) and the integrated GH values (P = 0.019). A similar significant enhancement of GH responses to exogenous GRH as compared to the control day was observed with the specific beta 1-adrenergic receptor-blocker atenolol in all seven subjects studied (four of whom also participated in the propranolol study). Both the peak GH response to a GRH bolus and the integrated GH values were significantly greater with atenolol (P = 0.019 for both). There was no difference in serum GH concentrations after beta-adrenergic receptor-blocking drugs during a three-hour sampling period before GRH administration compared to placebo. Our results support the concept that beta-adrenergic receptors may modulate either the release or action of hypothalamic somatostatin in the control of GH secretion in man. We suggest the effect is mediated by specific beta 1-adrenergic receptors.

Adrenergic beta-Antagonists↗
PubMed1987

Modulating actions of estradiol on gonadotropin-releasing hormone-stimulated prolactin secretion in postmenopausal individuals.

The temporal aspects of estrogen treatment on serum prolactin concentrations basally and in response to a 10 micrograms intravenous injection of gonadotropin-releasing hormone were assessed in eight postmenopausal women. The response of prolactin to gonadotropin-releasing hormone stimulation was compared with that of follicle-stimulating hormone and luteinizing hormone obtained simultaneously. Basal serum prolactin increased significantly (p less than 0.001) in response to estrogen treatment, and a positive correlation was found between the serum concentrations of estradiol and prolactin (r2 = 0.266; p = 0.0011). Gonadotropin-releasing hormone induced a significant increase in serum prolactin concentrations, which was greater after 5 to 10 days of estrogen treatment compared with that in the estrogen-depleted state (p = 0.031). No correlation was found between gonadotropin-releasing hormone-stimulated prolactin and luteinizing hormone or follicle-stimulating hormone release. These data demonstrate that estrogen treatment of previously hypoestrogenemic postmenopausal women potentiates gonadotropin-releasing hormone-stimulated prolactin release. Furthermore, our data suggest that the previously described paracrine interaction between the gonadotropins and lactotropes exerted by gonadotropin-releasing hormone does not appear to be mediated via increased gonadotropin release.

Estradiol↗
PubMed1987

Response of anterior pituitary cells to culture media.

We examined the ability of four commonly used culture media to support prolactin (PRL), growth hormone (GH), and adrenocorticotropic hormone (ACTH) release, as well as the inhibitory PRL response to dopamine. After a week of primary culture, rat anterior pituitary cells from both genders were studied over a 4 hour period. Whereas ACTH secretion was similar across the various media, PRL and GH release were lessened with M199 and F10, respectively. Dopamine inhibited PRL release under all media conditions which was inconsistant with the reported lack of a dopamine effect with RPMI-1640 medium. These data confirm the postulate that media culture conditions can determine the degree of expression of constituitive phenotypes in anterior pituitary cells.

Adrenocorticotropic Hormone↗
PubMed1987

Impact of intensive venous sampling on characterization of pulsatile GH release.

The effect of sampling intensity on quantitative properties of pulsatile growth hormone (GH) release was tested using an objective, statistically based pulse detection algorithm (Cluster). Seven normal young men had blood withdrawn at 5-min intervals for 24 h. The number of GH peaks/24 h (mean +/- SE) detected in the 5-min series (5.93 +/- 0.66) was significantly greater than the number of peaks documented in the constituent 10-min (3.45 +/- 0.28), 15-min (2.79 +/- 0.31), 20-min (2.86 +/- 0.64), 30-min (2.5 +/- 0.36), 45-min (2.21 +/- 0.21), and 60-min (1.93 +/- 0.23) series. The increased number of peaks detected with 5-min sampling reflected high-frequency pulsatile GH release occurring within the major GH secretory episodes. Both the mean widths and areas associated with peaks identified in the 5-min series were smaller than those documented with less intensive sampling. Peak amplitude did not change with sampling intensity. These data suggest that the major secretory episodes of GH release in normal young men encompass high-frequency GH secretory activity. That these high-frequency GH secretory events have not previously been described probably reflects the relatively infrequent sampling paradigms (e.g., every 20-30 min) commonly used in the past.

Adult↗
PubMed1987

Appraising the nature of luteinizing hormone secretory events in men.

We have appraised the nature of spontaneous luteinizing hormone (LH) secretory events in normal men by analyzing immunoactive LH concentrations in blood samples withdrawn at 5-min intervals for 24 h in eight healthy individuals. A novel discrete deconvolution algorithm was applied to determine apparent instantaneous LH secretory rates from these LH concentration series. These analyses unmasked unique attributes of spontaneous LH secretory events, which were represented as delimited momentary augmentations in endogenous LH secretory rates interspersed among intervals of relative secretory quiescence. For three different peak-detection thresholds (P = 0.02, = 0.01, and = 0.005), the frequency of LH secretory episodes was significantly greater than that of LH "pulses" judged from concentration data alone. Moreover, the total mass of LH released within discrete secretory episodes could account for approximately 90% of LH secreted during the day. This model of distinct, short-lived, burst-like secretion of LH has important implications for further investigations of the neuroendocrine regulation of gonadotropin secretion in humans.

Adult↗
PubMed1987

Actions of estradiol on discrete attributes of the luteinizing hormone pulse signal in man. Studies in postmenopausal women treated with pure estradiol.

We assessed the time-dependent impact of estradiol on properties of the luteinizing hormone (LH) pulse signal in 12 hypoestrogenemic postmenopausal volunteers studied basally and after 1, 5, 10, and 30 d of estradiol delivery via an intravaginal Silastic ring. Computerized analysis of the plasma LH time series revealed a significant decrease in LH pulse frequency within 24 h of estrogen treatment, followed by a secondary increase (days 5 and 10), and then a sustained decline (day 30) in LH pulsatility. Estradiol also significantly suppressed incremental and maximal (but not fractional) LH pulse amplitudes in a biphasic manner. In contrast, LH peak duration was invariant until day 30 of estradiol replacement. These observations indicate that the well recognized biphasic actions of estradiol on mean serum LH concentrations can be modeled in relation to specific and time-dependent alterations in LH pulse frequency and amplitude.

Administration, Intravaginal↗
PubMed1987

Effects of sex and age on the 24-hour profile of growth hormone secretion in man: importance of endogenous estradiol concentrations.

We undertook a study of the separate and combined effects of age and sex on the pulsatile pattern of GH secretion. The 24-h secretory profile of GH was generated by 20-min sampling in 10 young women (aged 18-33 yr), 10 young men (aged 18-33 yr), 8 postmenopausal women (aged greater than 55 yr), and 8 older men (aged greater than 55 yr). A computer-assisted pulse analysis program was used to assess both total GH secretion, as reflected in the 24-h integrated GH concentration (IGHC), and pulsatile secretion, as denoted by pulse frequency, duration, amplitude, and the fraction of GH secreted in pulses during the 24-h period (FGHP). IGHC was significantly greater in women than in men (P less than 0.025) and greater in the young than in the old (P less than 0.003). The mean pulse amplitude, duration, and FGHP were each greater in the young (P less than 0.006, P less than 0.03, and P less than 0.0001, respectively), but not significantly different between the sexes. The mean pulse frequency was not affected by sex or age. The serum concentration of free estradiol, but not free testosterone, correlated with IGHC (r = 0.46; P less than 0.005), pulse amplitude (r = 0.53; P less than 0.001), and FGHP (r = 0.59; P less than 0.0002). After correcting for the effects of estradiol, neither sex nor age influenced IGHC or mean pulse amplitude, while the effect of age on FGHP was reduced from 81% to 29%. Of the indices of GH secretion, FGHP had the strongest correlation (r = 0.43; P less than 0.006) with somatomedin-C. Somatomedin-C declined significantly with age in both sexes. Our results indicate that sex and age have independent and interrelated effects on GH secretion. These effects can be largely accounted for by corresponding variations in endogenous estradiol levels. These observations suggest an amplifying action of estradiol on the neuroendocrine regulation of pulsatile GH release.

Adolescent↗
PubMed1987

Augmentation of growth hormone secretion during puberty: evidence for a pulse amplitude-modulated phenomenon.

The augmentation of GH secretion that occurs during puberty has been attributed to changes in sex steroid levels that enhance the frequency and amplitude of GH pulses. To investigate the specific GH pulse characteristics responsible for such augmentation we analyzed the serum GH concentration profiles of 10 boys in Tanner stages I-II of sexual development (group A; aged 10 5/12-15 1/12 yr) and compared their GH pulse characteristics with those of 5 boys at Tanner stages IV-V of development (group B; aged 14 8/12-15 1/12 yr). We also reanalyzed previously reported data from 5 prepubertal boys (group C; aged 13 6/12-15 5/12 yr) before and after 10 weeks of treatment with testosterone enanthate (100 mg/4 weeks, im). Using a pulse detection algorithm that constrains the false positive pulse detection rate to less than 5% (Cluster), we found that group B boys had a significantly higher mean serum GH pulse amplitude compared to group A boys (17.1 +/- 2.6 vs. 8.6 +/- 1.7 ng/mL; P = 0.012), but both groups had the same mean GH pulse frequency (group B, 5.4 +/- 0.5 pulses/24 h vs. group A, 5.5 +/- 0.4 pulses/24 h; P greater than 0.05). Similar changes were found in group C boys before and after testosterone therapy; there was no significant change in GH pulse frequency (6.6 +/- 0.9 before vs. 7.6 +/- 0.5 pulses/24 h after treatment; P greater than 0.05), but there was a significant increase in the GH pulse amplitude after therapy (6.8 +/- 1.6 before vs. 15.4 +/- 2.4 ng/mL after treatment; P = 0.04). When the 24-h GH concentration profiles were analyzed using a mathematically distinct method for the estimation of pulse amplitudes, namely the Fourier expansion time series, we confirmed a significant increase in GH pulse amplitude with later stages of puberty and androgen treatment. We conclude that the augmentation in GH secretion that occurs during either spontaneous puberty or exogenous testosterone therapy is an amplitude-modulated phenomenon, relatively independent of changes in pulse frequency. Such an effect may be secondary to the action of sex steroid hormones modulating either the responsivity of somatotrophs to endogenous GH-releasing hormone, the amount of GH-releasing hormone secreted, or the tonic inhibitory tone of somatostatin.

Adolescent↗