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Naloxone Does not Reverse the Suppressive Effects of Testosterone Infusion on Luteinizing Hormone Secretion in Pubertal Boys^*

Departments of Pediatrics University of Michigan Ann Arbor, Michigan 48109-0718
Biostatistics University of Michigan Ann Arbor, Michigan 48109-0718
Internal Medicine University of Michigan, Ann Arbor, Michigan 48109-0718

Address all correspondence and requests for reprints to: Gad B. Kletter, M.D., University of Michigan, Division of Pediatric Endocrinology, MPB D3252, Box 0718, Ann Arbor, Michigan 48109-0718.

In this study we wished to test whether, and if so when, the suppressive effects of testosterone on LH and, by inference, GnRH secretion are mediated via endogenous opioid pathways during male pubertal maturation. As a preliminary study, we evaluated the acute effects of a 24-h infusion of testosterone (T) in eight pubertal boys with constitutional delay of growth in order to determine the optimal time for administration of naloxone. Eight additional pubertal boys received a saline infusion, followed 1 week later by a similar T infusion starting at 1000 h and lasting for 33 h. After 2 h of infusion (both saline and T), four iv boluses of saline were given hourly, and after 26 h of infusion, four hourly iv boluses of naloxone were given. Blood was obtained every 15 min for LH and every 30 min for T measurements. T infusion increased the mean T concentration by 3.8–fold (P < 0.001). Mean LH and LH pulse frequency were suppressed (P < 0.01), and the sleep-associated increase in LH secretion was abolished. Naloxone administration during the infusion of T did not reverse the suppression of LH secretion. Compared to the saline control period, mean LH was significantly lower during T infusion during the time naloxone boluses were given (4.5 ± 0.9 vs. 5.9 ± 1.1 IU/L, T infusion and naloxone boluses vs. saline respectively, P < 0.01). Although the suppression of LH pulse frequency remained significantly lower than that during the saline control period (0.23 ± 0.04 pulses/boy.h during T infusion and saline boluses; 0.33 ± 0.04 pulses/boy.h during T infusion plus naloxone boluses; 0.44 ± 0.06 pulses/ boy.h during saline infusion and saline boluses). Naloxone increased mean LH and LH pulse frequency only in the four older, more mature boys during the infusion of saline. Pituitary responsiveness to exogenous GnRH was not altered by infusion of T.

We conclude that acute administration of T suppresses LH secretion and, by inference, GnRH secretion at all stages of pubertal maturation in boys. These negative feedback effects, however, cannot be reversed by coadministration of naloxone, even in mid-to late pubertal boys who respond to naloxone with increased pulsatile secretion of LH. These studies suggest that during pubertal maturation in boys, endogenous opioid pathways do not play a major role in the regulation of the negative feedback effects of T.

^* This work was supported by NIH Grant HD-16000 and Clinical Research Center Grant MOl-RR-00042.

Received April 1, 1991.

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