REGULATION OF BIOLOGICALLY-ACTIVE DIMERIC INHIBIN-A AND INHIBIN-B FROM INFANCY TO ADULTHOOD IN THE MALE

Inhibins are glycoprotein members of the transforming growth factor-be ta family that have been implicated in the control of spermatogenesis by exerting a negative feedback on FSH secretion. In addition, locally produced inhibins may play a role in paracrine regulation of testicul ar function. Immunoassays were used to measure the two biologically ac tive dimeric forms of inhibin (inhibin A and B) in serum, seminal plas ma, and urine. To better define their actions, inhibins were measured in the male during infancy, sexual maturation, and senescence. Inhibin B but not A was measurable in the serum of male newborns, infants, ch ildren, and adults. In adult males, measurable levels of inhibin B wer e detected in the seminal plasma but not the urine. The circulating le vels of inhibin B increased shortly after birth and peaked at 4-12 mon ths of age (210 +/- 31 pg/mL). The concentration measured in the serum then decreased to a low of 81 +/- 12 pg/mL of inhibin B from 3-9 yr o f age followed by a gradual increase beginning with the onset of puber ty and reaching another peak of 167 +/- 20 pg/mL in males who were 20- 30 yr of age. Inhibin B levels then gradually declined with increasing age up through 90 yr of age. Serum levels of gonadotropins and total testosterone production were also measured in these same males. There was a brief increase in the gonadotropins (FSH and LH) during the few months of postnatal development, followed by a decrease to basal level s until the onset of puberty at 10-14 yr of age. Testosterone was also increased in the serum of infants from day 1 through 12 months of age , which decreased in young children but increased again following the elevation of gonadotropins during puberty. In adults aged 20-90 yr, se rum levels of inhibin B were inversely proportional to levels of FSH b ut not LH or testosterone. In males in which a semen analysis was perf ormed, those males with normal semen analysis had a significantly high er inhibin B levels, sperm production, and lower FSH levels than males with either oligospermia or nonobstructive azoospermia. The levels of Inhibin B found in circulation were a good marker for testicular func tion and could be useful in the diagnosis of patients with semen abnor malities or a complete absence of spermatogenesis. Because this glycop rotein is secreted in high amounts in the prepubertal testis up to 3 y r of age, inhibin B could potentially be used as a marker in the diagn osis of cryptorchidism and precocious puberty.