A novel mechanism for the modulation of luteinizing hormone receptor mRNA expression in the rat ovary.
Luteinizing hormone receptor (LHR) is a G-protein-coupled receptor that exerts its effects mainly through increased cAMP synthesis. Our previous studies have shown that a ovarian cytosolic protein, designated as LHR mRNA binding protein (LRBP) is an important regulator of the steady state levels of LHR expression. To test whether LHR mRNA expression is modulated by cAMP through LRBP activity, we used rolipram, a type IV phosphodiesterase inhibitor that is known to promote intracellular cAMP accumulation. On day 4 of pseudopregnancy, rats were treated with rolipram (1.25 mg/injection) to raise intracellular levels of cAMP. In order to maintain higher cAMP levels, up to four injections of rolipram were given, with the last injection 4 h before collecting the ovaries. Measurement of cAMP levels showed an increase (p< or =0.05) at 8, 12, and 24 h after rolipram injections at total dosages of 2.5, 3.75 and 5.0 mg/rat, respectively. Northern blot analysis of LHR mRNA showed that rolipram treatment also markedly reduced ovarian LHR mRNA levels by up to 75%. LHR mRNA binding activity of LRBP, assayed by RNA electrophoretic mobility shift analysis, using S-100 fractions from control or rolipram-treated ovaries showed increased LHR mRNA binding activity in the S-100 fractions from rolipram treated groups. These data indicate that chronic elevation of ovarian cAMP leads to a decreased expression of LHR mRNA with a concomitant increase in LHR mRNA binding activity of LRBP.
Peegel
H
H
Department of Obstetrics and Gynecology, 6428 Medical Science I, 1150 West Medical Center Drive, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Towns
R
R
Nair
A
A
Menon
K M J
KM
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011555:Pseudopregnancy / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D011974:Receptors, LH / Q000235:genetics*; D020889:Rolipram / Q000494:pharmacology
C402897:LRBP-1 protein, rat; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011974:Receptors, LH; D000242:Cyclic AMP; D020889:Rolipram