The interaction of gonadotropin-releasing hormone and estradiol on luteinizing hormone and prolactin gene expression in female hypogonadal (hpg) mice.
We have investigated the interaction of estrogen with GnRH on the regulation of LH subunit mRNA in female hypogonadal (hpg) mice receiving constant frequency and amplitude pulsatile GnRH treatment for up to 18 days. The level of cytosolic common alpha mRNA in female hpg mouse pituitaries was 45 +/- 6% of normal female littermate values, and treatment with pulsatile GnRH increased alpha mRNA to 40% above the normal value at 24 h and 2-4 times normal at 7 and 12 days (P less than 0.001); by 18 days levels had returned to those of untreated hpg controls. Concurrent treatment with estradiol (E2) did not affect those changes. However, in ovariectomized hpg mice the 2- to 4-fold rise in alpha mRNA was sustained for 18 days with GnRH treatment. E2 treatment alone for 7 and 12 days doubled alpha mRNA. LH beta mRNA levels in untreated female hpg mice were between 5-10% of normal values. Levels increased significantly (77 +/- 6.4%) 24 h after GnRH treatment and were normal at 7, 12, and 18 days. E2 together with GnRH did not affect the LH beta mRNA increase at 12 days, but reduced it to 45% of normal at 18 days. Ovariectomy did not alter the LH beta mRNA response to GnRH treatment, and E2 treatment alone did not increase LH beta mRNA. Serum LH concentrations were normalized by GnRH treatment at all times and did not increase in ovariectomized animals. LH release was prevented when E2 was combined with GnRH. Pituitary LH content in hpg mice was 20% of normal and increased gradually with GnRH treatment. Neither concurrent treatment with E2 nor ovariectomy affected the GnRH-induced synthesis of LH. PRL mRNA levels were 30-40% of normal littermate values in untreated female hpg mice, and pulsatile GnRH increased these to 70-80% of normal. E2 alone raised PRL mRNA slightly above normal values, although together with GnRH this rise was attenuated by about 40%. Pulsatile GnRH treatment of ovariectomized hpg mice did not increase PRL mRNA. E2 increased pituitary PRL content, and GnRH did not attenuate this aspect of E2 action. Serum PRL levels rose with E2 treatment at 7 and 12 days, and concurrent GnRH treatment prevented the rise at 12 days. We conclude the following: 1) The stimulatory action of pulsatile GnRH on the expression of both common alpha and LH beta mRNA is rapid (less than 24 h).(ABSTRACT TRUNCATED AT 400 WORDS)
Saade
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Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom.
London
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DR
Clayton
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RN
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D007006:Hypogonadism / Q000235:genetics* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000032:analysis / Q000097:blood / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D010052:Ovariectomy; D010902:Pituitary Gland / Q000032:analysis / Q000503:physiopathology / Q000648:ultrastructure; D010906:Pituitary Hormone-Releasing Hormones / Q000378:metabolism* / Q000494:pharmacology; D011388:Prolactin / Q000032:analysis / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011966:Receptors, LHRH / Q000032:analysis; D013997:Time Factors
D010906:Pituitary Hormone-Releasing Hormones; D012333:RNA, Messenger; D011966:Receptors, LHRH; D004958:Estradiol; D011388:Prolactin; D007986:Luteinizing Hormone