Gonadal steroids regulate rat anterior pituitary levels of TSH-releasing hormone- and pyroglutamyl-glutamyl-proline amide-like immunoreactivity.
The novel peptide, pyroglutamylglutamylprolineamide (pGlu-Glu-ProNH2, EEP), which has structural and immunological similarities to TRH (pGlu-His-ProNH2) has recently been shown to contribute to total TRH-like immunoreactivity (t-TRH-LI) detected in the rabbit prostate and rat and porcine anterior pituitary. This study was undertaken to determine the effects of gonadal steroids on t-TRH-LI and its components in the rat hypothalamus and pituitary. EEP-like immunoreactivity (EEP-LI) was separated from TRH-LI by ion exchange chromatography and detected by TRH RIA. Although male and female posterior pituitary and hypothalamic t-TRH-LI levels were similar, the mean t-TRH-LI in female anterior pituitaries was significantly lower than that in males, 10.3 +/- 2.9 pmol/g vs. 24.4 +/- 2.5 pmol/g (P < 0.01). Anion exchange analysis of control anterior pituitary samples distinguished two peaks of t-TRH-LI, corresponding to [125I]-TRH marker and [3H]-EEP markers. In control female anterior pituitaries EEP-LI accounted for 26.0 +/- 2.4% of t-TRH-LI, whereas in males it accounted for 43.3 +/- 5.3% of the total. Hypothalamic and posterior pituitary samples only contained t-TRH-LI corresponding to [125I]-TRH markers. There was no significant change in hypothalamic and posterior pituitary levels of t-TRH-LI after ovariectomy or orchidectomy. Anterior pituitary levels of t-TRH-LI, however, were increased by an estimated 6-fold after ovariectomy and 2-fold after orchidectomy. After ovariectomy, the proportions of t-TRH-LI accounted for by TRH-LI and EEP-LI were reversed in the female. EEP-LI now accounted for the majority of t-TRH-LI, constituting an increase of approximately 21-fold in pituitary EEP-LI levels. The changes in the levels of pituitary TRH-LI and EEP-LI induced by ovariectomy were reversed by 17-beta-estradiol. As in the ovariectomized samples EEP-LI was increased (2-fold) by orchidectomy. Both TRH-LI, which increased 1.6-fold, and EEP-LI were restored to control values after testosterone replacement. These findings confirm the hypothesis that pituitary TRH-LI and EEP-LI are regulated by gonadal status. The fact that these changes were not observed in the hypothalamus and posterior pituitary suggests that TRH-LI and EEP-LI have specific functional significance in the pituitary gland.
Royal Postgraduate Medical School, Department of Medicine, London, United Kingdom.
K O
KO
Akinsanya
M A
MA
Ghatei
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SR
Bloom
D000818:Animals; D000906:Antibodies; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004967:Estrogens / Q000097:blood; D005260:Female; D007031:Hypothalamus / Q000378:metabolism*; D007118:Immunoassay; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D004967:Estrogens; D013739:Testosterone; D004958:Estradiol; D013973:Thyrotropin-Releasing Hormone; C059697:pyroglutamyl-glutamyl-proline amide; C010452:estradiol-17 beta-benzoate; D011761:Pyrrolidonecarboxylic Acid