A novel testis-stimulating factor in familial male precocious puberty

Penelope K. Manasco, Penelope P. Feuillan, Kevin M. Barnes, Gordon B. Cutler, D. Lynn Loriaux, Barry D. Albertson, Mary E. Girton, Richard L. Diggs, John L. Doppman

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20 Scopus citations

Abstract

Background. Familial male precocious puberty is a gonadotropin-independent form of precocious puberty that occurs only in males. The cause of the disorder is unknown. To examine the hypothesis that the plasma of boys with familial male precocious puberty contains a novel stimulator of testicular testosterone production, we developed a bioassay using adult male cynomolgus monkeys. Methods. We collected plasma from 12 boys with familial male precocious puberty, 7 normal prepubertal boys of similar ages and with similar plasma gonadotropin levels, and 1 boy with hypogonadotropic hypogonadism and infused it into the testicular artery of adult male cynomolgus monkeys that had been pretreated with gonadotropin-releasing—hormone antagonist to inhibit the endogenous secretion of gonadotropins. Testicular venous effluent was collected at 15-minute intervals for 3 or 5 hours for the measurement of testosterone. Results. The mean (±SE) peak testosterone response, as compared with base line, was significantly greater in the monkeys infused with plasma from the 12 boys with familial male precocious puberty than in the monkeys infused with plasma from the 7 normal prepubertal boys and the boy with hypogonadotropic hypogonadism (385±51 vs. 184±25 percent, P<0.005) in the three-hour studies. Plasma from 92 percent of the boys with familial male precocious puberty and 12.5 percent of the normal prepubertal boys stimulated a response greater than 195 percent of base-line values. In the animals studied for five hours after receiving a second dose of antagonist, the mean peak testosterone response, as compared with base line, was significantly greater in the monkeys infused with plasma from three boys with familial male precocious puberty than in the monkeys infused with plasma from three normal prepubertal boys (363±81 vs. 115±6 percent, P<0.01). The mean area under the testosterone-response curve was significantly larger in the monkeys infused with plasma from the boys with familial male precocious puberty in the five-hour studies (154±34 vs.— 58±10 percent, P<0.005), but not in the three-hour studies. Conclusions. These findings support the presence of a circulating testis-stimulating factor in the plasma of boys with familial male precocious puberty. The production of such a factor would explain the biologic nature of the disorder. (N Engl J Med 1991; 324:227–31.).

Original languageEnglish (US)
Pages (from-to)227-231
Number of pages5
JournalNew England Journal of Medicine
Volume324
Issue number4
DOIs
StatePublished - Jan 24 1991

ASJC Scopus subject areas

  • Medicine(all)

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