Blockade of noradrenergic neurotransmission with diethyldithiocarbamic acid decreases the mRNA level of gonadotropin-releasing hormone in the hypothalamus of ovariectomized, steroid-treated prepubertal rats.
We have previously found that progesterone (P) augmented gonadotropin-releasing hormone (GnRH) mRNA levels in the hypothalamus of ovariectomized, estradiol-treated (OVX + E) prepubertal rats. In order to determine whether noradrenergic neurotransmission is involved in the stimulatory effect of P on GnRH gene expression, diethyldithiocarbamic acid (DDC, 500 mg/kg), a dopamine beta-hydroxylase inhibitor was administered i.p. 1 h before P (1 mg) injection into OVX + E treated rats, and the effect of DDC on the P-induced GnRH mRNA levels was examined. A single injection of P into OVX + E primed rats augmented norepinephrine (NE) content, while the administration of DDC effectively blocked the P-induced increase in NE content, along with the increase in dopamine content. Suppression of NE neurotransmission with DDC resulted in a marked decrease in the P-induced GnRH mRNA levels as well as GnRH release in vitro. These results clearly demonstrate that noradrenergic neurotransmission is involved in P-stimulated GnRH gene expression in the rat hypothalamus.
Kim
K
K
Department of Molecular Biology, College of Natural Sciences, Seoul National University, Korea.
Lee
B J
BJ
Cho
B N
BN
Kang
S S
SS
Choi
W S
WS
Park
S D
SD
Lee
C C
CC
Cho
W K
WK
Wuttke
W
W
D000818:Animals; D015152:Blotting, Northern; D004050:Ditiocarb / Q000494:pharmacology*; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation; D009435:Synaptic Transmission / Q000187:drug effects*
D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D004050:Ditiocarb; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine