title: Organizational role for testosterone and estrogen on adult hypothalamic-pituitary-adrenal axis activity in the male rat.
abstract: Organizational effects of testosterone during a critical period of neonatal life have major irreversible effects on adult sexual behavior. We have investigated whether perinatal androgen changes also affect another major sexually differentiated system, the hypothalamo-pituitary-adrenal axis. This was assessed in male rats who had been exposed to perinatal flutamide or 1,4,6-androstatriene-3,17-dione (ATD). Once the animals reached adulthood, an automated sampling system was used to collect blood from freely moving animals at 10-min intervals over 24 h, followed by a noise stress and then the administration of lipopolysaccharide (LPS). Perinatal flutamide- and ATD-treated rats not only had higher mean corticosterone levels and increased frequency and amplitude of corticosterone pulses over the 24 h compared with vehicle-injected controls, but they also showed markedly increased corticosterone responses to both noise and LPS. All parameters of increased hypothalamo-pituitary-adrenal activity resembled the normal physiological state of the intact adult female rather than that of the intact adult male rat. Furthermore, 3 h after LPS administration, both flutamide- and ATD-treated animals had markedly higher levels of corticotropin-releasing factor mRNA in the parvocellular paraventricular nucleus (PVN) and proopiomelanocortin mRNA in the adenohypophysis. Flutamide-treated rats also had a greater level of PVN arginine vasopressin mRNA. PVN glucocorticoid receptor mRNA levels were significantly lower in both the flutamide- and the ATD-treated male rats. These data highlight the importance of perinatal exposure to both testosterone and estrogen(s) on the development of a masculinized circadian corticosterone profile and stress-induced hypothalamo-pituitary-adrenal axis activity in the adult male rat.
authors.affiliation: Laboratories for Integrative Neuroscience and Endocrinology, Dorothy Hodgkin Building, Whitson Street, University of Bristol, Bristol BS1 3NY, United Kingdom.
authors.forename: J V
authors.initials: JV
authors.lastname: Seale
authors.forename: S A
authors.initials: SA
authors.lastname: Wood
authors.forename: H C
authors.initials: HC
authors.lastname: Atkinson
authors.forename: S L
authors.initials: SL
authors.lastname: Lightman
authors.forename: M S
authors.initials: MS
authors.lastname: Harbuz
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000733:Androstatrienes / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010913:Pituitary-Adrenal System / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000502:physiology*; D014156:Transcortin / Q000032:analysis
chemical_list: C115984:1,4,6-androstatrien-3,17-dione; D000733:Androstatrienes; D004967:Estrogens; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D001127:Arginine Vasopressin; D013739:Testosterone; D005485:Flutamide; D000324:Adrenocorticotropic Hormone; D014156:Transcortin; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone