Neonatal treatment of male monkeys with a gonadotropin-releasing hormone agonist alters differentiation of central nervous system centers that regulate sexual and skeletal development.
Male rhesus monkeys treated continuously with a GnRH agonist for the first 4 months of postnatal life exhibited a delay in the onset of puberty and an attenuated peripubertal rise in testosterone (T) secretion. The objectives of the current study were to determine whether these effects on sexual development were permanent and whether the hypothalamic-pituitary-testicular axis was functioning normally in these animals as adults. Neonatal GnRH agonist treatment delays but does not permanently block sexual maturation in male monkeys. Treated animals that did not show a pubertal rise in serum T during the breeding season of their 4th year exhibited a seasonal but subnormal elevation of serum T during the subsequent breeding season. Growth of the skeleton was diminished as evidenced by shorter adult crown-rump, tibia, and femur length and reduced bone mineral density of the humerus and lumbar spine. The magnitude of the serum LH and T response to iv pulses of GnRH [50 ng/kg body weight (BW)] and naloxone (1 mg/kg BW) did not differ between control and treated animals during the nonbreeding or breeding season at 6 yr of age. Conversely, treated animals showed a subnormal serum LH and T response to N-methyl-D,L-aspartic acid (5 mg/kg BW iv) during the nonbreeding season. These data suggest that adult monkeys treated neonatally with a GnRH agonist exhibit subnormal sensitivity of the central nervous system to one or more excitatory amino acids (e.g. aspartate or glutamate). Thus, abolishing neonatal activation of the pituitary-testicular axis with a GnRH agonist may permanently alter differentiation of central nervous system centers that are either involved in GnRH secretion or govern this process.
Department of Physiology, Morehouse School of Medicine, Yerkes Regional Primate Research Center, Atlanta, Georgia 30310-1495.
D R
DR
Mann
M A
MA
Akinbami
K G
KG
Gould
J M
JM
Tanner
K
K
Wallen
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001846:Bone Development / Q000502:physiology*; D002490:Central Nervous System / Q000254:growth & development* / Q000502:physiology; D004542:Ejaculation / Q000502:physiology; D004558:Electric Stimulation; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood; D008253:Macaca mulatta; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D012098:Reproduction; D012621:Seasons; D012741:Sexual Maturation / Q000502:physiology*; D013739:Testosterone / Q000097:blood; D017329:Triptorelin Pamoate / Q000031:analogs & derivatives*
D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D009270:Naloxone; D013739:Testosterone; C019176:Tryptal; D016202:N-Methylaspartate; D007986:Luteinizing Hormone