A protective role for testosterone in adjuvant-induced arthritis.
We have investigated the role of the gonadal steroids testosterone (T) and progesterone in modulating: (1) the onset and severity of adjuvant-induced arthritis (AA), (2) the response of the hypothalamo-pituitary-adrenal (HPA) axis, and (3) the levels of plasma prolactin and anterior pituitary prolactin messenger ribonucleic acid (mRNA) in the rat. Male rats were castrated (CSX) and received either no T, low T or high T delivered using silastic implants. In a second study experimental groups comprised CSX/AA, CSX/AA + progesterone or CSX/AA + progesterone + T. The time of onset was sooner and the severity of AA was greater in CSX rats. Inflammation was prevented by T replacement. Endogenous plasma T levels were decreased in AA rats. In control animals with AA there was an increase in pro-opiomelanocortin (POMC) mRNA in the anterior pituitary and of plasma corticosterone, and a decrease in corticotrophin-releasing factor (CRF) mRNA. These changes in the HPA axis of AA and CSX/AA rats were reversed by T replacement. These data suggest that T has an important protective effect on the progress and severity of AA. This was reflected by a reversal of the neuroendocrine changes of the HPA axis. Progesterone treatment alone had no effect on the severity of the disease. Prolactin mRNA in the anterior pituitary was decreased in the CSX and in the CSX/AA group but was not altered by AA. Plasma prolactin was raised in AA but T replacement did not reduce these elevated levels despite the absence of disease. Thus, prolactin provides a poor indicator of inflammation, suggesting that it may not be a potent pro-inflammatory compound in AA.
Harbuz
M S
MS
University Department of Medicine, Bristol Royal Infirmary, UK.
Perveen-Gill
Z
Z
Lightman
S L
SL
Jessop
D S
DS
D000704:Analysis of Variance; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D017403:In Situ Hybridization; D008297:Male; D009919:Orchiectomy; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011333:Pro-Opiomelanocortin / Q000235:genetics; D011374:Progesterone / Q000008:administration & dosage / Q000502:physiology; D011388:Prolactin / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000097:blood / Q000494:pharmacology / Q000502:physiology*
D012333:RNA, Messenger; D013739:Testosterone; D011374:Progesterone; D011333:Pro-Opiomelanocortin; D011388:Prolactin; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone