The present study aimed to determine the influence of thyroid status on the timing of the pubertal resurgence in gonadotrophin-releasing hormone pulse generator activity [tracked by circulating luteinising hormone (LH) levels] in male rhesus monkeys. Six juvenile monkeys were orchidectomised and then treated with the antithyroid drug, methimazole, from 15-19 months until 36 months of age, at which time thyroxine (T(4)) replacement was initiated. Four additional agonadal monkeys served as controls. Blood samples were drawn weekly for hormonal assessments. Body weight, crown-rump length and bone age were monitored at regular intervals. By 8 weeks of methimazole treatment, plasma T(4) had fallen sharply, and the decline was associated with a plasma thyroid-stimulating hormone increase. In controls, plasma LH levels remained undetectable until the pubertal rise occurred at 29.3 +/- 0.2 months of age. This developmental event occurred in only half of the methimazole-treated animals before 36 months of age when T(4) replacement was initiated. The hypothyroid state was associated with a profound arrest of growth and bone maturation, but increased body mass indices and plasma leptin levels. T(4) replacement in methimazole-treated monkeys was associated with the pubertal rise in LH in the remaining three animals and accelerated somatic development in all six animals. Although pubertal resurgence in LH secretion occurred at a later chronological age in methimazole-treated animals compared to controls, bone age, crown-rump length and body weight at that time did not differ between groups. There were no long-term differences in plasma prolactin between groups. We conclude that juvenile hypothyroidism in male primates causes a marked delay in the pubertal resurgence of LH secretion, probably occasioned at the hypothalamic level. Whether this effect is meditated by an action of thyroid hormone directly on the hypothalamus or indirectly as a result of the concomitant deficit in somatic development remains to be determined.

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The present study examined whether a transient thyroid hormone (T 4 ) deficit during infancy in male monkeys would compromise the arrest of luteinising hormone (LH) secretion during the infantjuvenile transition, and/or interfere with the pubertal resurgence of LH. Animals were orchidectomised and thyroidectomised (n = 3; Tx) or sham Tx (n = 3) within 5 days of birth. T 4 replacement was initiated in two Tx monkeys at age 19 weeks to reestablish a euthyroid condition. Blood samples were drawn weekly for hormone assay. Body weight, crown-rump length, and bone age were assessed throughout the study. Within a week of Tx, plasma T 4 declined to undetectable levels and, by 6-8 weeks of age, signs of hypothyroidism were evident. Transient hypothyroidism during infancy failed to prevent either arrest of LH secretion during the infant-juvenile transition or the pubertal resurgence of LH secretion, both of which occurred at similar ages to sham Tx animals. Although body weight exhibited complete catch-up with T 4 replacement, crown-rump length and bone age did not. Thus, bone age at the time of the pubertal LH resurgence in Tx animals was less advanced than that in shams. Although Tx did not influence qualitatively the pattern of gonadotrophin secretion, LH levels during infancy and after pubertal LH resurgence were elevated in Tx monkeys. This was not associated with changes in LH pulse frequency and amplitude, but half-life (53 versus 65 min) of the slow second phase of LH clearance was greater in Tx animals. These results indicate that hypothalamic mechanisms dictating the pattern of gonadotrophin-releasing hormone release from birth to puberty are not dependent on T 4 action during infancy, and fail to support the notion that onset of puberty is causally coupled to skeletal maturation. They also indicate that LH renal clearance mechanisms may be programmed in a T 4 dependent manner during infancy. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptPostnatal development of the hypothalamic-pituitary-gonadal axis in higher primates may be divided into three distinct phases: infantile, juvenile and pubertal, although, in man, the infancy and the juvenile phases of development are separated by childhood (1). Infancy in the male primate is characterised by an active period of gonadotrophin and testosterone secretion but, during the transition from infancy to childhood in boys, and directly to the juvenile phase of development in monkeys, gonadotrophin and testosterone secretion decline to low levels characteristic of subsequent prepubertal development (2,3). This quiescent period in the activity of the pituitary-gonadal axis continues until there is a resurgence of gonadotrophin secretion that leads to the initiation of puberty at the end of juvenile development (2,3). This postnatal pattern of activity in the pituitary-gonadal axis is considered to be dictated by parallel changes in pulsatile release of gonadotrophin-releasing hormone (GnRH) by the hypothalamus (2,3).Although our current un...

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In humans, circulating leptin levels are low in early childhood and rise until puberty, whereas the reverse occurs for the soluble leptin receptor (sOB-R). In women, leptin remains high and sOB-R remains low, but in men leptin declines after adolescence and sOB-R increases. These observations suggest that leptin may regulate the production of sOB-R, and that the increased testosterone in adolescent boys may be responsible for the gender differences in leptin and sOB-R. To test this hypothesis, leptin was administered continuously to agonadal juvenile male monkeys for 16 days. No change in sOB-R was observed. Intact juvenile male monkeys were given pulsatile doses of gonadotropins for a period of 7 weeks to induce precocious puberty and assess the effect on plasma testosterone, leptin, and sOB-R. By 4 weeks testosterone had reached adult levels. No changes were observed in leptin, but by week 4, sOB-R was higher than pretreatment values and remained higher at week 7. These data suggest that leptin may not play a significant role in regulating the production of sOB-R and that gender differences in sOB-R in humans may be driven by the increased production of testosterone at puberty in males.