Pituitary-testicular axis abnormalities in immature male hypothyroid rats

The pituitary-testicular disturbances which follow the onset of hypothyroidism were studied in immature male Wistar rats rendered hypothyroid by treatment with methimazole (MMI) given in drinking water, starting at 40 days of age. Half of the animals continued on MMI (MMI group) up to 140 days of age; the remaining rats were withdrawn MMI at 100 days and injected thereafter s.c. with 3 micrograms of T3 daily, during the last 40 days (MMI + T3 group). Ten rats were used as controls (C group). Hypothyroidism induced in immature animals significantly decreased serum T4, T3, LH, PRL, and testosterone levels, and also impaired the normal growth of body and sex accessory glands. T3 replacement therapy helped to normalize serum hormonal levels, but the body and sex accessory gland weights were not fully corrected. Hypothyroidism also reduced the [125I]LH/hCG binding sites of testicular homogenates. T3 replacement was not able to improve the binding; nonetheless, the hormone-receptor affinity constant remained unaltered among the groups. Leydig cell responsiveness to hCG stimulation in vitro (0-82 nM) showed impaired testosterone production in the MMI group (25% of that found in the C group) and also in the MMI + T3 group (80% of that found in the C group). These data demonstrate that induction of hypothyroidism in the immature male rat leads to alterations in serum LH, PRL and testosterone levels, and suggest that thyroid hormones have a modulating action on the testis as far as LH-mediated testosterone secretion is concerned.