Sex differences in the pituitary-adrenal response following acute antidepressant treatment in sheep.
BACKGROUND
Depression is more prevalent in women than in men, and therapeutic responses may also differ between the sexes. In addition, abnormal regulation of the hypothalamic-pituitary-adrenal (HPA) axis is more common in depressed women.


OBJECTIVE
To further examine these phenomena, the present study was designed to investigate whether sex differences exist in the HPA axis responses of male and female sheep following acute antidepressant administration.


METHODS
Two commonly prescribed antidepressants, imipramine (a tricyclic antidepressant, TCA; 2.0 and 5.0 mg/kg) and sertraline (a selective serotonin reuptake inhibitor, SSRI; 0.5, 2.0 and 5.0 mg/kg) were administered to gonadectomized male and female sheep via acute subcutaneous injection. Treatment order was randomized. Jugular blood was sampled for the measurement of prolactin, adrenocorticotropin (ACTH), and cortisol by radioimmunoassay.


RESULTS
Treatment with sertraline resulted in a comparable increase in prolactin secretion in male and female sheep. However, sertraline stimulated ACTH and cortisol secretion in females but not in males, a sexually dimorphic effect that was independent of circulating sex steroids. Treatment with imipramine had no effect on prolactin, ACTH or cortisol levels in male or female sheep.


CONCLUSIONS
These data suggest that the HPA axes of females are more sensitive to the stimulatory effects of serotonin following acute treatment with the SSRI, sertraline.
Broadbear
Jillian H
JH
Department of Physiology, Monash University, 3800, Victoria, Australia.
Hutton
Lisa C
LC
Clarke
Iain J
IJ
Canny
Benedict J
BJ
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000097:blood; D012727:Sex Characteristics; D012756:Sheep
D000928:Antidepressive Agents; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D006854:Hydrocortisone