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Biomedical subjects

A D Rogol

Publications and source records attributed to A D Rogol.

247 records · Page 14Linked to original sources

Pulsatile secretion of gonadotropins and prolactin in male marathon runners. Relation to the endogenous opiate system.

We tested the hypothesis that sustained, strenuous physical training alters the neuroendocrine regulation of pulsatile gonadotropin and/or prolactin secretion in men. Blood was sampled at 20-minute intervals over 8 hours in five endurance-trained men after a 10-15 mile run in the middle of the active training season, and in 11 nonendurance trained normal controls. In these two groups, basal patterns of physiologically pulsatile secretion of LH, FSH, and prolactin (PRL) were not significantly different in relation to the following parameters: mean serum concentration of each of the three hormones (N = 25 samples); areas under the hormone concentration vs. time curves; fractional, incremental, and absolute pulse amplitudes; and pulse frequency, or periodicity. To test for enhanced suppressive effects of endogenous opiates in trained male marathon runners, subjects were administered the potent opiate-receptor antagonist, naltrexone (1 mg/kg). This antagonist significantly stimulated pulsatile LH secretion by increasing mean serum LH values from 10.94 to 13.58 mIU/ml (P = 0.007); area under the LH concentration vs. time curve increased from 5370 to 6510 mIU/ml X 8 hours (P = 0.05) and, pulse frequency rose from 2.8 to 4.9 pulses/8 hours (P = 0.006). Naltrexone also enhanced pulse frequency of FSH secretion from 3.4 to 5.4 pulses/8 hours (P = 0.009), but did not alter serum prolactin concentrations. None of these responses differed significantly from those in normal sedentary controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Spectrum of the pulsatile characteristics of LH release in normal men.

To assess the spectrum of LH pulse characteristics in normal men, blood samples from 36 individuals were drawn at 20-minute intervals for 8 hours. The subsequent immunoactive LH concentrations were analyzed by computer algorithms to delineate the frequency and amplitude characteristics of pulsatile LH secretion. The absolute range for LH pulse frequency estimated by a modified threshold method was 1-6 pulses/8 hr, with a mean (+/- SEM) of 3.36 +/- 0.17 (median -3)pulses/8 hr. The distribution differed significantly from a Gaussian pattern. The mean LH pulse amplitude expressed as a percent increase above nadir was 92.1 +/- 6.1 (median-91.5%). When LH pulse amplitude was defined as an increment (mIU/ml) above nadir, the mean value was 5.13 +/- 0.4 (median -4.8) mIU/ml. These two expressions of amplitude were positively correlated (P less than 0.01), while the incremental (mIU/ml) pulse amplitude correlated inversely with pulse frequency (P less than 0.01). To examine the influence of more intensified rates of venous sampling on the spectrum of LH pulse properties, blood was sampled at 4-minute intervals for 8 hours in a subgroup of 13 men. Under these conditions, estimated LH pulse frequency was significantly higher, with a mean of 10.31 +/- 1.87 (median -9) pulses/8 hr compared with 20-minute sampling in the same individuals (P less than 0.001). Although the estimates of LH pulse frequency at 4-minute and 20-minute sampling intervals were significantly correlated (P less than 0.01), the dispersion of the LH pulse frequency estimates was considerably larger at more rapid rates of sampling. There was an absolute range of 2-20 pulses/8 hr for the 4-minute sampling, and 1-6 pulses/8 hr for the 20-minute sampling in the same individuals. This increase in LH pulse frequency and the broader dispersion of the range of frequencies estimated at 4-minute compared with 20-minute sampling intervals were confirmed using either another pulse detection algorithm, or separate criteria designed to adjust false-positive error rates in relation to sampling intensity. It was concluded that eugonadal men exhibit a broad spectrum of pulsatile LH characteristics, and the range of LH pulse attributes is even greater at more intensive rates of venous sampling. The results of this study in normal men demonstrate that a wider dispersion of physiologic LH pulse characteristics must be recognized in man.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

The effect of long-term opiate antagonist administration to pubertal boys.

To test further the hypothesis that opiatergic pathways controlling gonadotropin production may be functional during early to mid adolescence, nine pubertal boys with bone ages ranging from 10 to 15 were given the long-acting opiate antagonist, naltrexone, for up to 4 weeks. Urinary gonadotropin measurements were assessed before, during, and after drug administration. In three early to mid-pubertal boys who received naltrexone for 3 to 4 weeks, LRH testing was also performed. No evidence of a stimulatory FSH or LH response to naltrexone was found in any of the patients evaluated. The data do not support the operation of an opiate-mediated mechanism in the control of pubertal onset in man.

Adolescent↗

Appraising the instantaneous secretory rates of luteinizing hormone and testosterone in response to selective mu opiate receptor blockade in late pubertal boys.

The pulsatile properties of gonadotropin and testosterone release were examined before and after chronic mu opiate receptor blockade with naltrexone, 50 mg every other day, in four normal boys in late puberty (ages 14 8/12 to 15 1/12 years). The nature of spontaneous secretory events was appraised for immunoactive LH and testosterone in blood withdrawn every 20 minutes for 24 hours, using a novel, discrete deconvolution algorithm to estimate apparent instantaneous secretory rates. The application of this methodology revealed that the frequency of discrete LH instantaneous secretory rates increased after mu opiate receptor blockade (P = 0.011). More strikingly, all parameters of testosterone secretory events responded significantly to mu opiate receptor blockade, including increases in mean estimated secretory rate (+47%, P = 0.02), testosterone pulse frequency (+ 64%, P less than 0.001) and amplitude (+ 20%, P = 0.027). Correspondingly, decreases in testosterone interpulse secretory intervals (-35%, P = 0.001), secretory pulse duration (-19%, P = 0.042) and interpulse valley duration (-35%, P = 0.006) also were noted. There was a prominent diurnal rhythm in testosterone secretion with maximal values in the morning and late evening, and marked reductions in the afternoon, sometimes to prepubertal levels. This variation in the testosterone secretory profile paralleled that of LH. In response to naltrexone, the FSH concentration series showed a significant increase in the mean FSH concentration (+ 18%) P = 0.003) and mean peak amplitude (+ 15%, P = 0.002). These data provide indirect evidence of functional coupling of the opiate system with the hypothalamic GnRH pulse generator.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Physiologic attributes of the luteinizing hormone pulse signal in the human. Cross-validation studies in men.

The performance of two new statistically based, independently formulated, endocrine peak detection methodologies (Cluster and Detect) were tested on the same large set of physiologic LH pulsations. Serum LH concentrations were determined in blood samples withdrawn at 5-minute intervals for 24 hours in eight healthy young men. The subsequent comprehensive LH time series were subjected to Cluster and Detect analysis, each constrained to an alpha level of 0.01 or 0.05. Under both circumstances, computer estimates of physiologic LH pulse frequency by the two separate algorithms were statistically indistinguishable. Moreover, the two distinct methodologies were concordant not only in relation to the original 5-minute sampling series but also with respect to the constituent 10-, 15-, 20-, 30-, and 45-minute sampling data. The cross-validation of these two mathematically independent methodologies has permitted delineation of the detailed spectrum of spontaneous LH pulse properties within individual men and among different males under basal physiologic conditions.

Adult↗

Alterations in the pulsatile properties of gonadotropin secretion in alcoholic men.

The functional characteristics of the hypothalamic-pituitary-testicular axis were examined quantitatively in 10 chronic alcoholic men without hepatic dysfunction or clinical nutritional deficiencies. Spontaneous gonadotropin pulsatility was analyzed in blood sampled every 20 minutes over a 24-hour period 3 to 16 days after abstinence from alcohol and again 29 to 39 days later. The numbers of LH and FSH pulses per 24 hours were normal in these alcoholic men compared with controls. However, we found increased mean 24-hour concentrations of immunoactive LH (P = 0.012) and FSH (P = 0.018), increased peak heights for LH (P = 0.035) and FSH (P = 0.004), decreased fractional LH (P = 0.002) and FSH (P = 0.044) pulse amplitudes and increased interpulse valley mean LH (P = 0.010) and FSH (P = 0.018) concentrations. Serum levels of total testosterone, total estradiol and estrone were normal, whereas concentrations of free testosterone and free estradiol were increased. Pituitary release of LH and FSH was normal in response to low (5-micrograms) and high (95-micrograms) doses of GnRH given intravenously. The present observations indicate that in chronically alcoholic men, acute abstinence from ethanol is associated with elevated circulating concentrations of immunoactive gonadotropins in the presence of intact spontaneous gonadotropin pulsatility, preserved pituitary responsiveness to exogenous GnRH, and increased concentrations of free testosterone and free estradiol. Such findings are consistent with alterations in the endogenous feedback actions of sex steroid hormones in this setting.

Adult↗

Effects of opioid receptor blockade on luteinizing hormone (LH) pulses and interpulse LH concentrations in normal women during the early phase of the menstrual cycle.

To determine the role of endogenous opioid peptides in regulating pulsatile luteinizing hormone (LH) release in the early follicular phase of the menstrual cycle of eumenorrheic women, we evaluated serum LH concentrations in blood collected every 10 min for 12 h in 27 women each studied during two menstrual cycles: (1) without pretreatment and (2) following oral administration of naltrexone, a mu opiate receptor blocking agent, at a dose of 1.0 mg/kg. Pulsatile LH release was assessed by the CLUSTER algorithm. The mean (+/- SE) integrated serum LH concentration (IU/L/min) increased following the administration of naltrexone (4715 +/- 298) in comparison to the control day (3997 +/- 381; p = 0.0008). The mean number of LH pulses (/12 h) detected on the naltrexone day (10.3 +/- 0.3) was higher than on the control day (8.9 +/- 0.4; p = 0.0068). Mean maximal LH peak height (IU/L) was greater on the naltrexone (7.8 +/- 0.5) vs control (6.7 +/- 0.5) days (p = 0.0064) as was the interpulse valley mean serum LH concentration (IU/L; 6.3 +/- 0.4 vs 5.0 +/- 0.4; p = 0.0013). No difference was noted in the mean incremental LH pulse amplitude (IU/L; 1.9 +/- 0.1 vs 2.1 +/- 0.1; p = 0.13), or peak duration (min; 40 +/- 1.8 vs 45.0 +/- 2.4; p = 0.06). Mean LH peak area (IU/L/min) was greater on the control (45.0 +/- 2.4) vs naltrexone (40 +/- 1.8) days (p = 0.0475).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Unusual heterogeneity of circulating prolactin in an acromegalic.

Plasma from a 69-year-old acromegalic woman with hyperprolactinemia (350-570 ng/ml) was chromatographed on dextran gel. Three components of immunoactive prolactin were observed. Component I eluted with an apparent molecular weight (MWapp) of greater than 100,000, Component II with MWapp of 45,000 and Component III with MWapp of 21,500 daltons (indistinguishable from monomeric pituitary prolactin). Components I and II comprised more than 70% of the total circulating prolactin. All components had similar activities in immunoassays and in receptor assays. Components II and III maintained their elution positions on re-chromatography. Component I whether frozen or stored at 4 C eluted in the position of Component II on rechromatography, suggesting that Component I is a loosely-bound oligomer of Components II or III, or Component III loosely-bound to another constituent of plasma. The gel chromatography pattern for immunoactive growth hormone was indistinguishable from that of other acromegalic patients.

Acromegaly↗

Arginine-induced insulin and growth hormone secretion in children with nutritional rickets.

We evaluated arginine-induced insulin and growth hormone (GH) secretion in ten children with vitamin D deficiency rickets and compared these values with those of eight age-matched control children. All rachitic children had biochemical (increased serum alkaline phosphatase activity and decreased calcium x phosphate product) and clinical evidence for rickets. After an intravenous infusion of arginine-HCl (10% solution, 0.5 g/kg), blood samples were obtained for the measurement of serum insulin and GH concentrations. The mean insulin level 30 min after the start of the infusion was 22.2 +/- 17.1 microU/ml for the rachitic children. This value is significantly below that for the normal children, 63.4 +/- 38.7 microU/ml (p = 0.004). Neither the fasting insulin level nor any others after the arginine infusion differed significantly from those for the control children. There were no significant differences in the fasting or the arginine-stimulated GH levels between the rachitic and control children. The concentrations of insulin-like growth factors did not differ between the two groups.

Alkaline Phosphatase↗

Congenital anosmia: detection thresholds for seven odorant classes in hypogonadal and eugonadal patients.

Detection thresholds for a representative from each of seven odorant classes (putrid, pepperminty, ethereal, camphoraceous, pungent, musky, floral) were determined by double-blind smell testing of seven normal males, six normal females, 6 patients with uncomplicated congenital anosmia and 13 patients with the syndrome of congenital anosmia and hypogonadotropic hypogonadism (the Kallmann syndrome, olfactogenital dysplasia). The median detection thresholds did not differ significantly between hypogonadal and eugonadal anosmics for any of the odorants, suggesting that the endocrine deficit does not result from inadequate rhinencephalic input to brain centers controlling gonadotropin release. Phenylethylmethylethylcarbinol (PEMEC), a stable chemical of the floral class, was detecred at very low concentrations (10(-6) to 10(-8) M in water) by all normals tested. Since no patient with congenital anosmia was able to distinguish even undiluted PEMEC from water, we suggest that this compound is the material of choice for convenient, rapid and objective testing of the sense of smell (cranial nerve I).

Adolescent↗

Apparent self-limited androgen excess in a 4 year-old male.

We describe a 4 year-old male with significant virilization, but no source of endogenous or exogenous androgen excess after extensive testing. Evaluation of androgen receptor function, 5 alpha-reductase activity, steroid hormone secretion patterns, and androgen metabolite concentrations were also within the normal range. Over a 10 month period there was spontaneous resolution of the physical and behavioral signs of androgenization. We postulate a self-limited process of androgen production which may represent a yet undefined pattern of sexual precocity in males.

Body Height↗