title: Predominant suppression of follicle-stimulating hormone β-immunoreactivity after long-term treatment of intact and castrate adult male rats with the gonadotrophin-releasing hormone agonist deslorelin.
abstract: Gonadotrophin-releasing hormone (GnRH) agonists are used to treat gonadal steroid-dependent disorders in humans and to contracept animals. These agonists are considered to work by desensitising gonadotrophs to GnRH, thereby suppressing follicle-stimulating hormone (FSH) and luteinising hormone (LH) secretion. It is not known whether changes occur in the cellular composition of the pituitary gland after chronic GnRH agonist exposure. Adult male Sprague-Dawley rats were treated with a sham, deslorelin, or deslorelin plus testosterone implant for 41.0 ± 0.6 days. In a second experiment, rats were castrated and treated with deslorelin and/or testosterone. Pituitary sections were labelled immunocytochemically for FSHβ and LHβ, or gonadotrophin α subunit (αGSU). Deslorelin suppressed testis weight by two-thirds and reduced plasma FSH and LH in intact rats. Deslorelin decreased the percentage of gonadotrophs, although the effect was specific to the FSHβ-immunoreactive (-ir) cells. Testosterone did not reverse the deslorelin-induced reduction in the overall gonadotroph population. However, in the presence of testosterone, the proportion of gonadotrophs that was FSHβ-ir increased in the remaining gonadotrophs. There was no effect of treatment on the total LHβ-ir cell population, although the loss of FSHβ in bi-hormonal cells increased the proportion of mono-hormonal LHβ-ir gonadotrophs. The castration-induced plasma LH and FSH increases were suppressed by deslorelin, testosterone or both. Castration increased both LH-ir and FSH-ir without increasing the overall gonadotroph population, thus increasing the proportion of bi-hormonal cells. Deslorelin suppressed these increases. Testosterone increased FSH-ir in deslorelin-treated castrate rats. Deslorelin did not affect αGSU immunoreactivity, suggesting that the gonadotroph population per se is not eliminated by deslorelin, although the ability of gonadotrophs to synthesise FSHβ is compromised. We hypothesise that the FSH dominant suppression may be central to the long-term contraceptive efficacy of deslorelin in the male.
authors.affiliation: Neurobiology Program and Department of Zoology and Physiology, University of Wyoming, Laramie, WY 82071, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Smith
authors.forename: C S
authors.initials: CS
authors.lastname: Asa
authors.forename: B S
authors.initials: BS
authors.lastname: Edwards
authors.forename: W J
authors.initials: WJ
authors.lastname: Murdoch
authors.forename: D C
authors.initials: DC
authors.lastname: Skinner
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism*; D052681:Gonadotrophs / Q000187:drug effects / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006727:Hormone Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D017329:Triptorelin Pamoate / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D006727:Hormone Antagonists; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D005640:Follicle Stimulating Hormone; C066438:deslorelin