Central inhibition of gonadotropin-releasing hormone secretion in the growth-restricted hypogonadotropic female sheep

Growth retardation induced by dietary restriction results in hypogonadotrop ism, and thus, puberty is delayed. The present studies determined 1) whethe r reduced LH secretion in the growth-retarded condition is due to a reducti on in the frequency and/or in the amplitude of GnRH secretion, and 2) wheth er the mechanism regulating LH secretion is being actively inhibited via ce ntral mechanisms. To deter mine whether GnRH pulse frequency and/or amplitu de are reduced during growth restriction, blood samples were simultaneously collected from pituitary portal blood for GnRH and from jugular blood for LH determinations over a 4-h period in ovariectomized lambs (52 wk of age) that were either growth restricted (28 kg; n = 8) or growing normally (60 k g; n = 7). As expected, the growth-restricted females were hypogonadotropic and exhibited a long LH interpulse interval compared with the normally gro wing females. However, although the GnRH interpulse interval was longer in the growth-restricted lambs compared with that in the normally growing lamb s, the pattern of GnRH secretion did not directly correspond with that of L H secretion in the growth-restricted group. In addition, high amplitude GnR H pulses that coincided with LII pulses and small, low amplitude GnRH pulse s without a concomitant LIT pulse occurred. The second study tested the hypothesis that diet-induced hypogonadotropism is the result of actively inhibited central mechanisms by investigating the effects of the nonspecific central nervous system inhibitor, sodium pentob arbital, on pulsatile LH secretion in the growth-restricted lamb. Serial bl ood samples were collected from 11 ovariectomized lambs that were maintaine d at weaning weight (similar to 20 kg) by reduced diet. After a 4-h pretrea tment period, six of the lambs were anesthetized with sodium pentobarbital for 4 h; the other five lambs were untreated and served as controls. Pentob arbital anesthesia reduced the LW interpulse interval (increased the freque ncy) and increased mean LW, levels. These findings suggest that during growth restriction hygogonadotropism ari ses from a central inhibition of GnRH neurons and is manifest as a decrease in both frequency and amplitude of GnRH pulses.