NEONATAL-HYPOTHYROIDISM PERMANENTLY ALTERS FOLLICLE-STIMULATING-HORMONE AND LUTEINIZING-HORMONE PRODUCTION IN THE MALE-RAT

Transient neonatal hypothyroidism, induced with the goitrogen 6-n-prop yl-2-thiouracil (PTU), results in dramatic increases in both testis si ze and sperm production in the adult rat. The observed increases in te stis size and function occur in the presence of normal circulating tes tosterone levels. However, circulating gonadotropin levels are chronic ally reduced by 30-50% at all times in treated males. To better unders tand the permanent reduction in serum gonadotropin levels following tr ansient neonatal hypothyroidism, we conducted a series of experiments to evaluate pituitary and hypothalamic function in the adult male PTU- treated rat. PTU treatment led to a significant reduction in GnRH-stim ulated LK production. Castration resulted in 3.9- to 8.5-fold increase s in circulating gonadotropin levels in both treated and control males ; however, the absolute increases were significantly reduced in treate d males. In contrast to circulating levels, pituitary gonadotropin con tents did not increase in treated males after castration. PTU treatmen t did not lead to a reduction in the density of either luteotropes or folliculotropes, and both cell types increased in size and density aft er castration. The relative concentrations of both gonadotropin beta-s ubunit messenger RNAs increased more slowly in treated males than in c ontrols after castration. Thus, although treated rats have the intrins ic ability to produce normal circulating levels of LH and FSH, gonadal feedback and an overall reduction in gonadotrope synthetic ability co mbine to produce the chronically reduced circulating levels of these h ormones.