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To determine potential mechanisms by which androgens alter gonadotropin secretion and elimination in the pubertal male, we administered the potent nonsteroidal androgen receptor blocking agent, flutamide, to eight males with Tanner IV or V genital development. Venous blood samples were obtained every 10 min for 24 h and assayed for LH by a sensitive and high-precision fluorimmunoassay. Subjects were studied before and after the administration of flutamide. Deconvolution analysis was used to assess specific pulsatile LH secretory characteristics and estimate LH production and metabolic clearance rates quantitatively. After antagonism of endogenous androgen action, mean 24-h serum LH concentrations increased significantly. An increased mean 24-h LH production rate, without evident changes in serum LH half-life, accounted for the increase in average serum LH levels. The increased daily secretion rate of LH was in turn due to both an augmented mass of LH released per secretory episode and increased frequency of secretory events. There was no demonstrable change in the maximal rate of LH secretion attained within each secretory event. Serum concentrations of total testosterone, free-testosterone, and 17 beta-estradiol all increased during blockade of androgen action. Administration of the antiandrogen had no measurable effect on the pituitary response to a single maximally effective dose of exogenous gonadotropin releasing hormone (GnRH). These results indicate that, in the late pubertal male, endogenous androgen exerts negative feedback control of gonadotropin secretion primarily at a hypothalamic site reflected by regulation of the frequency of pulsatile LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

We have used the technique of deconvolution analysis to determine if abnormalities in growth hormone (GH) secretion or metabolic clearance underlie the observed alterations in circulating hormone concentrations in a group of seven prepubertal males with constitutional delay of growth (SHORT-DBA). The results were compared with data obtained from 13 healthy, short prepubertal males (SHORT) and 11 healthy prepubertal male subjects of normal stature (NORMAL). Although the mean 12-h overnight GH production rates were invariant among the groups (8.0 +/- 1.0 versus 7.3 +/- 0.7 versus 6.7 +/- 1.2 micrograms/L, NORMAL versus SHORT versus SHORT-DBA for all comparisons), different secretory mechanisms were operative. The secretory burst half-duration (time interval of the secretory event at half-maximal amplitude) of the SHORT-DBA subjects (26 +/- 1 min) was greater (p = 0.02) than that of the SHORT group (20 +/- 1 min); values for both the SHORT and SHORT-DBA subjects were indistinguishable from that of NORMAL controls (22 +/- 2). Both the mass of GH released per secretory episode and the maximal rate of hormone secretion were less (p < or = 0.02 and the p < 0.01, respectively) for the SHORT-DBA subjects [16 +/- 2 micrograms/unit of body distribution volume (Lv) and 0.6 +/- 0.1 microgram/Lv/min, respectively] compared with those of the NORMAL (26 +/- 2 micrograms/L, and 1.1 +/- 0.1 micrograms/Lv/min, respectively) and SHORT (28 +/- 4 micrograms/Lv and 1.3 +/- 0.2 micrograms/Lv/min, respectively) groups; values for the latter two groups were indistinguishable.(ABSTRACT TRUNCATED AT 250 WORDS)

Overnight growth hormone (GH) concentrations obtained by frequent venous sampling of 20 healthy, short prepubertal boys were evaluated using the objective pulse detection algorithm, CLUSTER. The resulting pulsatile characteristics were compared with those of 11 healthy prepubertal boys of normal stature and with those of nine prepubertal children with documented GH deficiency. Although no significant differences of pulsatile GH release were found between the normal and short subjects, a subset of the short prepubertal boys with significantly delayed skeletal ages had subnormal sum of GH pulse areas and sum of GH pulse amplitudes. The finding of a significant correlation in all subjects between growth velocity and the sum of GH pulse amplitudes is important, as the results are compatible with the hypothesis that alterations of amplitude-modulated GH release underlie the pathophysiology of suboptimal growth in some short prepubertal children.

We measured the oxygen consumption, carbon dioxide production, and respiratory quotient during the combustion of a known mass of anhydrous ethanol and methanol to assess the accuracy of an open-circuit flow-through system. Continuous measurements were made of the mass of alcohol burned, the velocity of gas flow through the apparatus, and simultaneous measurements of the fractional concentration of oxygen, carbon dioxide and nitrogen of the inlet and outlet gas using paramagnetic oxygen analyzer, infrared carbon dioxide meter, and mass spectrometer. Standard respiratory and stoichiometric equations were used to calculate the oxygen consumption, carbon dioxide production and RQ for the mass of absolute alcohol combustion per unit time. In a series of 12 consecutive laboratory experiments (on 7 days), the measured values of gas exchange (similar to the rate of respiratory gas exchange by an infant of 1-4 kg) were in agreement within 5% of the true values for ethanol and methanol combustion, confirming the validity of the open-circuit method. The paramagnetic oxygen analyzer and the mass spectrometer gave similar oxygen consumption results and differed very little when the rate of absolute alcohol combustion was used to quantify the accuracy of the complete measurement system. A positive measurement error was observed for the carbon dioxide production results from both the IR meter and mass spectrometer, with the result that the respiratory quotient measurements were 3.4-4.7% higher than the true value. The mass spectrometer gave more precise oxygen consumption results, whereas smaller variance of carbon dioxide production measurements was observed using the infrared CO2 meter.(ABSTRACT TRUNCATED AT 250 WORDS)