| Summary: | Developmental changes within the hypothalamus are necessary for maturation of
the reproductive neuroendocrine axis. Recent reports have implicated several neuronal
networks in this process, but genes involved in their regulation have not been elucidated.
Using a well-established model for nutritional induction of precocious puberty,
objectives were to 1) use microarray technology to examine changes in gene expression
within the arcuate nucleus (ARC) of the hypothalamus in pre-pubertal heifers fed high or
low-concentrate diets, and 2) determine if high-concentrate diets are required for
nutritional induction of precocious puberty. In Experiment 1, early-weaned, cross-bred
heifers were fed either a high-forage/low-gain (HF/LG; 0.45 kg/d) or a highconcentrate/
high-gain (HC/HG; 0.91 kg/d) diet for 91 d. Analysis of microarray data
indicated that 346 genes were differentially expressed (P < 0.05) between HC/HG and
HF/LG heifers. Expression of three key metabolic genes [neuropeptide Y (NPY), agoutirelated
protein (AGRP), and growth hormone receptor (GHR)] observed to be
differentially expressed in the microarray analysis was investigated further by quantitative PCR. Real-time RT-PCR indicated that expression of NPY, AGRP and
GHR was lower (P < 0.05) in HC/HG compared to HF/LG heifers. In contrast,
concentrations of insulin (P < 0.05), IGF-1 (P < 0.002) and leptin (P = 0.1) were greater
in HC/HG compared to HF/LG. For Experiment 2, 48 heifers were used in 2 replicates
(24 heifers/replicate) in a 2 x 2 factorial design to examine the roles of diet type (HF vs
HC) and rate of gain (LG, 0.45 kg/d vs HG, 0.91 kg/d) on age at puberty. Heifers were
fed HC/HG, HC/LG, HF/HG or HF/LG (n = 12/group) for 14 wk, and then switched to a
common growth diet (0.68 kg/d) until puberty. Heifers in both HG groups reached
puberty at a younger age (54.5 ± 1.8 wk) than heifers in both LG groups (60.2 ± 1.9 wk;
P < 0.04). A marked increase (P < 0.01) in serum concentrations of leptin occurred in
HC/HG heifers between 24 and 30 wk of age. This increase in circulating leptin was not
observed in other groups. Overall, results indicate that nutritional regulation of
reproductive neuroendocrine development involves the control of NPY, AGRP and GHR
expression. The abrupt increase noted for circulating leptin in heifers fed HC/HG diets,
if timed and sustained appropriately, could represent an important temporal cue for
activation of the neuroendocrine system and the onset of puberty.
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