Gonadotropin-induced up- and down-regulation of rat ovarian LH receptor message levels during follicular growth, ovulation and luteinization.
Induction of follicular growth by PMSG is associated with increased ovarian LH receptor content, whereas the preovulatory surge of LH decreases LH binding sites, followed by a secondary increase in receptor numbers coincident with corpora lutea formation. Based on the recently reported LH receptor cDNA sequence, we have performed a reverse transcription-polymerase chain reaction to obtain LH receptor cDNA clones and generated a 32P-labeled cRNA probe to examine the dynamic changes in ovarian LH receptor mRNA levels during gonadotropin induction of follicular growth, ovulation and luteinization. Northern blot analysis of ovary RNA revealed hybridization signals of about 7.0, 4.2, 2.5 and 1.8 kb, with no hybridization to nongonadal tissues. PMSG increased the intensity of all four LH receptor messages at 24 h, preceding an increase in LH receptor number, with peak LH receptor mRNA and receptor content observed at 52 h. Treatment with hCG resulted in decreased LH receptor binding and mRNA levels by 6 h after injection, with maximal inhibition (greater than 85%) of message at 12 to 24 h after hCG treatment. Subsequently, LH receptor message levels increased again at 3 days after hCG, concomitant with increased [125I]hCG binding. A further increase in LH receptor content, but not message levels, was observed 5 days after hCG. These results demonstrate that the induction of LH receptors by PMSG is preceded by increased LH receptor mRNA levels. Furthermore, ligand-induced down-regulation of the LH receptor following an ovulatory dose of hCG is associated with decreased LH receptor message content, followed by increases in LH receptor message levels and binding sites during subsequent luteinization. Thus, the up- and down-regulation of ovarian LH receptors during follicle growth, ovulation and luteinization is probably due, at least in part, to changes in receptor message modulation.
LaPolt
P S
PS
Dept. of Reproductive Medicine, University of California, San Diego, La Jolla 92093.
Oikawa
M
M
Jia
X C
XC
Dargan
C
C
Hsueh
A J
AJ
D000818:Animals; D006063:Chorionic Gonadotropin / Q000378:metabolism / Q000494:pharmacology*; D003338:Corpus Luteum / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology*; D009693:Nucleic Acid Hybridization; D006080:Ovarian Follicle / Q000187:drug effects / Q000502:physiology; D010053:Ovary / Q000187:drug effects / Q000502:physiology*; D010060:Ovulation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011974:Receptors, LH / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
D006063:Chorionic Gonadotropin; D006064:Gonadotropins, Equine; D012333:RNA, Messenger; D011974:Receptors, LH