We have evidence suggesting that neonatal activation of the pituitary- testicular axis is a critical event in the process of sexual and behavioral maturation in male primates. Monkeys treated as neonates with a gonadotropin-releasing hormone (GnRH)-agonist to suppress testicular function exhibited differences in social behavior during the second year of life, a delay or retardation of testicular development during the peripubertal period and reduced male mountings during the non-breeding season of their third year of life. The proposed study is an effort to expand our understanding of the importance of neonatal testosterone as an organizational influence on sexual and behavioral processes in male primates. There are two components to this proposal: an adult component involving 5-year-old male monkeys treated as neonates with a GnRH-agonist and an infant component involving the development of an additional cohort of neonatal hypogonadotropic-hypogonadal animals using a potent GnRH- antagonist. With the adult component, we will determine whether the deleterious effects of suppressing neonatal pituitary-testicular function on sexual and aggressive behavior under conditions of high and low intermale competition are altered by neonatal treatment with a GnRH- analogue. Efforts will be made to define the site(s) (hypothalamus, pituitary or testis) of the physiological defect and determine whether the FSH-inhibin negative feedback loop is functionally normal in GnRH-agonist- treated monkeys. We will also perform a detailed evaluation of the fertility of these animals. In the infant component, we will attempt to confirm the effect of blocking neonatal activation of the pituitary- testicular on sexual maturation using a GnRH-antagonist. The importance of neonatal testosterone in this process will be assessed by treating one group of infants simultaneously with the GnRH-antagonist and testosterone. The effect of treatment on the developmental pattern of pituitary and gonadal hormone secretion, on growth and maturation of the skeletal system and on sexual maturation will be determined. The development of male typical behavior and adult sexual behavior will be compared between animals treated with the GnRH-antagonist alone or in combination with testosterone therapy. The proposed study will increase our understanding of developmental mechanisms that govern sexual and behavioral development in male primates and the role that neonatal testosterone plays in this process.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD026423-02
Application #
3327881
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1989-12-01
Project End
1994-11-30
Budget Start
1990-12-01
Budget End
1991-11-30
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Morehouse School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
Atlanta
State
GA
Country
United States
Zip Code
30310
Mann, David R; Plant, Tony M (2002) Leptin and pubertal development. Semin Reprod Med 20:93-102
Mann, D R; Akinbami, M A; Gould, K G et al. (2002) Leptin and thyroxine during sexual development in male monkeys: effect of neonatal gonadotropin-releasing hormone antagonist treatment and delayed puberty on the developmental pattern of leptin and thyroxine secretion. Eur J Endocrinol 146:891-8
Mann, D R; Akinbami, M A; Lunn, S F et al. (2000) Endocrine-immune interaction: alteractions in immune function resulting from neonatal treatment with a GnRH antagonist and seasonality in male primates. Am J Reprod Immunol 44:30-40
Mann, D R; Akinbami, M A; Gould, K G et al. (2000) Seasonal variations in cytokine expression and cell-mediated immunity in male rhesus monkeys. Cell Immunol 200:105-15
Herman, R A; Jones, B; Mann, D R et al. (2000) Timing of prenatal androgen exposure: anatomical and endocrine effects on juvenile male and female rhesus monkeys. Horm Behav 38:52-66
Mann, D R; Akinbami, M A; Gould, K G et al. (2000) A longitudinal study of leptin during development in the male rhesus monkey: the effect of body composition and season on circulating leptin levels. Biol Reprod 62:285-91
Mann, D R; Lunn, S F; Akinbami, M A et al. (1999) Effect of neonatal treatment with a GnRH antagonist on development of the cell-mediated immune response in marmosets. Am J Reprod Immunol 42:175-86
Mann, D R; Howie, S; Paulsen, D F et al. (1998) Changes in lymphoid tissue after treatment with a gonadotropin releasing hormone antagonist in the neonatal marmoset (Callithrix jacchus). Am J Reprod Immunol 39:256-65
Prince, F P; Mann, D R; Fraser, H M (1998) Blockade of the hypothalamic-pituitary-testicular axis with a GnRH antagonist in the neonatal marmoset monkey: changes in Leydig cell ultrastructure. Tissue Cell 30:651-61
Gould, K G; Akinbami, M A; Mann, D R (1998) Effect of neonatal treatment with a gonadotropin releasing hormone antagonist on developmental changes in circulating lymphocyte subsets: a longitudinal study in male rhesus monkeys. Dev Comp Immunol 22:457-67

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