Glucoprivic Regulation of Puberty Onset

Abstract

The purpose of our studies was to determine 1) if rats experience hypoglycemia during diet-restriction when puberty is delayed, and 2) if histaminergic pathways mediate glucoprivicinduced delay in puberty onset. Plasma blood glucose was measured in Experiment 1 at 60-min intervals for 4h after a single meal and for 2h before the next meal in diet-restricted (n=6) compared to ad libitum-fed females (n=5). Diet-restricted rats demonstrated decreased blood glucose in pre-meal samples, relative to ad libitum-fed rats. These data suggest that daily hypoglycemia may delay onset of puberty during diet-restriction. They also suggest that dietrestricted rats resemble food deprived rats, at least for a portion of the day, and that an overlap may exist in the mechanism by which diet-restriction and food deprivation suppress reproductive function. In Experiment 2, first estrus was determined during 2DG-induced glucoprivation, in the presence and absence of a histamine antagonist, a-fluoromethylhistidine (FMH), in previously diet-restricted rats with delayed puberty. During a 72h refeeding period, female rats were treated with either saline (sc) + aCSF (200 nl, 3V, n=8), saline+ FMH (2.24 ?mol/rat/day, 3V, n=8), 2DG (400 mg/kg, every 6h, sc) + aCSF (n=9), or 2DG + FMH (n=l 1). Rats receiving 2DG/aCSF and 2DG/FMH had delayed first estrus (7.3 � 1.1 and 6.8 � 1.4 days, respectively), compared to the control group (4.4 � 0.3 days). Fewer 2DG/FMH rats had first estrus compared to 2DG/aCSF rats ( 4/11 vs. 6/9). These data suggest that 2DG-induced glucoprivation suppresses onset of puberty. Reducing brain histamine levels potentiated this effect, suggesting a role for brain histamine in metabolic regulation of reproductive function in the developing animal.