Pituitary corticotroph function during the stress hyporesponsive period in neonatal rats

Rats undergo a period in early postnatal development during which they exhibit a reduced response to stress (stress-hyporesponsive period, SHRP). SHRP is marked by a reduced capacity to secrete adrenocorticotropin (ACTH) and corticosterone in response to stressful stimuli. To characterize pituitary responsiveness during this period, we examined the release of ACTH from cultured pituitary cells derived from rats at different ages. Corticotrophs were studied from animals before (day 1 postnatally), during (days 6 and 11) and after (days 16, 20 and adult) SHRP. Direct stimulation of dispersed pituitary cells, with increasing concentrations of synthetic corticotropin-releasing factor (CRF; 1 x 10(-12) to 1 x 10(-8) M), produced significant ACTH release at all ages tested. The greatest maximal release was observed for cells isolated from animals at 6 and 11 days of age (in the midst of SHRP). CRF-stimulated ACTH release from cells obtained just prior to (day 1) or immediately following (days 16 and 20) the hyporesponsive period was dramatically reduced (relative to cells from adult animals). SHRP is, therefore, not due to diminished intrinsic corticotroph responsiveness. In fact, pituitary cells derived from animals in SHRP exhibited enhanced ACTH secretion relative to cells from animals outside SHRP. This enhanced secretion was manifested as both an increased basal (unstimulated) release of ACTH as well as an increased maximal release of ACTH at saturating concentrations of CRF.