Ca. Lamar et al., REGULATION OF GONADOTROPIN-RELEASING-HORMONE (GNRH) SECRETION BY HEMEMOLECULES - A REGULATORY ROLE FOR CARBON-MONOXIDE, Endocrinology, 137(2), 1996, pp. 790-793
Recent studies suggest that carbon monoxide (CO), which is produced in
significant quantities in many brain regions including the hypothalam
us, may function as a neurotransmitter. The purpose of the present stu
dy therefore was to access whether CO is capable of regulating the sec
retion of the hypothalamic releasing factor, gonadotropin-releasing ho
rmone (GnRH). To this end, medial basal hypothalami were obtained from
estrogen-primed ovariectomized adult rats and incubated in vitro for
a 1 hour preincubation period followed by a 30 minute incubation with
either vehicle or test compounds. The media was then collected for GnR
H determination by RIA. Hematin, a heme molecule cleaved by heme oxyge
nase (HO) to yield CO, dose-dependently stimulated GnRH release with 5
0 mu M being the lowest effective dose. The effect of hematin was not
due to a toxic effect as all groups responded to KCL stimulation at th
e end of the experiment. The effect of hematin required HO cleavage as
evidenced by the fact that the HO inhibitor, zinc protoporphyrin IX (
ZnPP), blocked the effect of hematin on GnRH release. The effect of he
matin appeared to be due to its conversion to CO, as the CO scavenger
molecule, hemoglobin, completely reversed the effect of hematin. Final
ly, the effect of hematin did not appear to be due to the generation o
f the other HO-generated product (biliverdin) since biliverdin dose-de
pendently inhibited GnRH release. Taken as a whole, the present studie
s provide evidence that CO is capable of modulating hypothalamic GnRH
release in the female rat, suggesting that CO may function as a neurot
ransmitter in the hypothalamus.