Galanin is coexpressed in a subset of gonadotropin-releasing
hormone (GnRH) and growth hormone-releasing hormone (GHRH) neurons
in the brain and has an important role in the neuroendocrine
regulation of gonadotropin and growth hormone secretion. Our
overall goal has been to understand the functional significance
of galanin as a cotransmitter with GnRH and GHRH in the regulation
of these important physiologic processes. To this end, we studied
the regulation of galanin's expression in GnRH and GHRH neurons
under a variety of physiologic and experimental conditions.
Using double-label
in situ hybridization and computerized image
analysis, we observed that in GnRH neurons, galanin's expression
is increased over the course of development in both sexes. Galanin
achieves a higher basal expression in GnRH neurons in females,
and it is sexually differentiated in the adult as a result of
the differential exposure to testosterone during the neonatal
critical period. Galanin is induced in GnRH neurons coincident
with and subsequent to the proestrous luteinizing hormone surge
(reflecting the combined action of estradiol and progester-one)
acting indirectly on GnRH neurons through a synaptic relay.
Galanin's expression in GnRH neurons is inhibited during lactation,
when the neuroendocrine reproductive axis is relatively quiescent.
In GHRH neurons, the expression of galanin is also induced over
the course of development in both sexes. Galanin's expression
in GHRH neurons in the adult is sexually differentiated, but
in this case, its expression is higher in males than females,
reflecting the stimulatory effect of testosterone on galanin
in the male. Galanin's expression in GHRH neurons is induced
by growth hormone (GH), whereas the absence of GH leads to a
reduction of galanin mRNA in these same cells. On the basis
of these observations, we conclude that galanin is an important
target for regulation by many hormones, and we postulate that
as a cotransmitter, galanin acts presynaptically to modulate
the secretion of GnRH and GHRH, possibly by altering their pulsatile
release patterns, which in turn influences the release of the
gonadotropins and GH from the pituitary.
