Blockade of Neonatal Activation of the Pituitary-Testicular Axis: Effect on Peripubertal Luteinizing Hormone and Testosterone Secretion and on Testicular Development in Male Monkeys*

Abstract

The objective of this study was to examine the effect of blockade of neonatal activation of the pituitary-testicular axis, using a GnRH agonist, on sexual development in male rhesus monkeys. Monkeys were treated with either a GnRH agonist (10 micrograms/day; n = 8) or vehicle (n = 9) for 112 days using osmotic minipumps beginning at 10-13 days of age. In control monkeys serum LH and testosterone concentrations during the first 3 postnatal months were similar to those in adults; they then declined to very low levels. GnRH agonist administration caused an immediate and precipitous decline in serum LH and testosterone concentrations to very low levels, and both remained low throughout the rest of the agonist administration period. Neither group had any significant elevation in serum LH or testosterone concentrations during the next 2 yr. In the control monkeys serum LH and testosterone began to rise during the third year, with a rapid increase occurring during the fall coincident with the breeding season. This peripubertal rise of LH and testosterone secretion was associated with rapid enlargement of the testes and the appearance of sperm in ejaculates. The monkeys who had received GnRH agonist had subnormal serum LH and testosterone increases, and testicular enlargement was also attenuated compared to that in the control animals during the third year of life. Semen samples were recovered from only 50% of the GnRH agonist-treated monkeys during this period, and the sperm count per ejaculate was suppressed. The serum LH responses of the GnRH agonist-treated monkeys to an iv bolus dose of GnRH (5 micrograms/kg BW) during the third year were normal. These results suggest that the induction of reversible hypogonadotropin-hypogonadism in neonatal male monkeys alters subsequent testicular development and peripubertal endocrine changes. Thus, neonatal activation of the pituitary-testicular axis may be a critical developmental event in the process of sexual development in male primates.

Sexual maturation in male rhesus monkeys: importance of neonatal testosterone exposure and social rank

“…We reported previously that administration of a GnRH-A for the first 4 months of postnatal life either delayed or attenuated the peripubertal increase in LH and testosterone secretion, and testicular enlargement in male rhesus monkeys (Mann et al 1989). In the male marmoset, treatment with a GnRH antagonist (the same one used in the current study) from birth until 4 months of age, reduced the pubertal increase in serum LH and testosterone (Lunn et al 1994).…”

“…If puberty was not achieved in year 4, then puberty was delayed until the subsequent breeding season. Peripubertal adolescent male rhesus monkeys, regardless of rank or treatment, do not become sexually mature during the non-breeding season, but the achievement of reproductive competence is confined to the autumn breeding season (Mann et al 1989, and current study). Body weight or the achievement of a critical body mass may have a role in the process of sexual maturation, but may be subservient to the more critical factors of rank, treatment and season.…”

“…In several non-primate species, neonatal brain-pituitary-testicular activity has a role in the masculinization of the central nervous system, determination of Sertoli cell number, maturation of feedback systems regulating gonadotrophin secretion, development of the immune system, and social and sexual behavior (Goy & McEwen 1980, Huhtaniemi et al 1986, Baum et al 1990, van den Dungen et al 1990, Mann & Fraser 1996. In primates, neonatal events have been found to influence the timing of puberty and peripubertal and adult gonadotropin and testosterone secretion (Mann et al 1989, Lunn et al 1994. It is important to understand the significance of this period for the development of the hypothalamic-pituitary-testes axis, as the frequency of reproductive disorders in boys and men has increased over the past 50 years (Sharpe 1993(Sharpe , 1994.…”

“…Treated animals had either an attenuated pubertal increase in secretion of luteinizing hormone (LH) and testosterone and testicular enlargement during year 4, or puberty was delayed for 1 year (Mann et al 1989. As adults, they had reduced basal LH and testosterone secretion, and retarded skeletal growth and development (Eisler et al 1993.…”

Development and sexual selection in primates

“…The timing of puberty in males is influenced by neonatal testosterone (Mann et al , 1989;Eisler et al, 1993, Lunn et al, 1994, and conditions during the infant stage thus have consequences for pubertal development. The timing of sexual maturation may also be affected by the social environment.…”