Enkephalin appears to modulate several aspects of reproductive functio
n in female rats. The purpose of this study was to determine if lactat
ion influences preproenkephalin gene expression in one or more hypotha
lamic nuclei known to be involved in maternal or reproductive behavior
and prolactin secretion. Lactating rats were killed on day 3 (LAG 3)
or day 10 (LAG 10) of lactation, Controls consisted of regular 4-day c
ycling rats that were killed on diestrous day 1, with 9 to 12 females
per group. We used in situ hybridization histochemistry to assess prep
roenkephalin gene expression in individual cells in the medial preopti
c nucleus, anterior, medial and posterior arcuate nucleus, magnocellul
ar and parvocellular aspects of paraventricular nucleus, and ventromed
ial nucleus. Preproenkephalin mRNA in the anterior arcuate nucleus inc
reased to reach significance (P < 0.05) at day 10 of lactation. Levels
in the medial arcuate nucleus increased significantly (P < 0.001) by
day 3 of lactation (LAG 3) and remained elevated on day 10 (LAG 10). N
o significant differences between lactating and control rats were dete
cted in preproenkephalin mRNA levels in the posterior arcuate nucleus,
medial preoptic nucleus or in the ventromedial nucleus. Substantial l
evels of preproenkephalin mRNA were found in the paraventricular nucle
us, particularly in a limited region of the magnocellular portion. How
ever, these levels did not change with lactation. These data provide e
vidence for differential regulation of the preproenkephalin gene durin
g lactation. This change may contribute to lactational hyperprolactine
mia and suppressed GnRH secretion, leading to reproductive acyclicity.