Effects of antiandrogens and ethane dimethane sulphonate (EDS) on gene expression, free subunits, bioactivity and secretion of pituitary gonadotrophins in male rats.
In the male rat, testosterone has been shown to regulate gonadotrophin synthesis and secretion under experimental conditions such as castration or gonadotrophin-releasing hormone (GnRH) antagonist with or without testosterone. The present study aims at clarifying the effects of non-steroidal antiandrogens, Casodex and flutamide, and ethane dimethane sulphonate (EDS) on the regulation of gonadotropin synthesis and secretion. To enable a direct comparison within this study to expected effects of testosterone, a GnRH antagonist-treated group and a castrated group were included. The gene expression of the subunits was correlated with changes in the pituitary and plasma content of immunoreactive luteinizing hormone (LH) and follicle-stimulating hormone (FSH), free subunits and pituitary content of in vitro bioactive LH and FSH. Groups of ten male rats each received the following treatments for 7 days: (1) vehicle; (2) castration; (3) EDS (75 mg/kg); (4) GnRH antagonist (Cetrorelix 250 micrograms/kg/day), (5) Casodex (20 mg/kg/day) or (6) flutamide (20 mg/kg/day). The effectiveness of testosterone deprivation was demonstrated by the reduction of weight in androgen-dependent organs such as epididymides and seminal vesicles in the treated groups. Treatment with flutamide, EDS or castration significantly increased (p < 0.05) serum levels of LH, FSH and alpha-subunit, whereas serum gonadotrophin levels were decreased in the GnRH antagonist-treated group. alpha-Subunit mRNA levels were elevated in the castrated, EDS and flutamide group and LH-beta mRNA levels were increased in the castrated and EDS group. FSH-beta mRNA levels were increased in the castrated group and decreased in the GnRH antagonist group, but remained unchanged in the flutamide and EDS group.(ABSTRACT TRUNCATED AT 250 WORDS)
Gromoll
J
J
Institute of Reproductive Medicine of the University, Münster, Germany.
Weinbauer
G F
GF
Simoni
M
M
Nieschlag
E
E
D000726:Androgen Antagonists / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D005485:Flutamide / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000235:genetics / Q000378:metabolism; D037201:Follicle Stimulating Hormone, beta Subunit; D015870:Gene Expression / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D006065:Gonadotropins, Pituitary / Q000235:genetics / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008297:Male; D008698:Mesylates / Q000494:pharmacology*; D009570:Nitriles; D009919:Orchiectomy; D010902:Pituitary Gland / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000494:pharmacology / Q000502:physiology; D014105:Tosyl Compounds
D000726:Androgen Antagonists; D000813:Anilides; D037201:Follicle Stimulating Hormone, beta Subunit; D006065:Gonadotropins, Pituitary; D008698:Mesylates; D009570:Nitriles; D012333:RNA, Messenger; D014105:Tosyl Compounds; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D005485:Flutamide; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C053541:bicalutamide; C002994:ethylene dimethanesulfonate