ADRENOCORTICOTROPIN SECRETION BY FETAL SHEEP ANTERIOR AND INTERMEDIATE LOBE PITUITARY-CELLS IN-VITRO - EFFECTS OF GESTATION AND ADRENALECTOMY

Immunoreactive (ir) ACTH is present in the fetal sheep intermediate lo be (IL) as well as the anterior pituitary (AP). It is not clear whethe r fetal IL cells can secrete irACTH and if gestational age and glucoco rticoids influence the secretion ACTH from these tissues in a similar fashion. Therefore, we examined the control of irACTH secretion by IL cells, whether the responsiveness of AP and IL cells to arginine vasop ressin (AVF) and CRH changes during gestation, and whether withdrawal of adrenal steroids by adrenalectomy influences AP and IL responses. C ultured pituitary cells were studied from intact fetuses at an immatur e (n = 5; 108 +/- 5 days) and a mature (n = 8; 139 +/- 0 days) stage, from mature fetuses 3 weeks after bilateral adrenalectomy (n = 6), and from neonatal lambs within 16 h of birth (n = 6). Secretion of irACTH was determined by RIA of incubation medium obtained during 3-h exposu re of cells to vehicle, AVP, CRH, or both. In all cases, IL cells secr eted measurable irACTH. The IL cells of immature fetuses responded to CRH (133 +/- 8% increase over basal secretion), AVP (52 +/- 6%), and C RH plus AVP (244 +/- 8%). In contrast, IL cells from mature fetuses re sponded only to CRH (160 +/- 20%) or CRH plus AVP (259 +/- 44%), as di d cells from mature adrenalectomized fetuses (CRH, 356 +/- 70%; CRH pl us AVP, 627 +/- 100%). Secretion from neonatal IL cells was not signif icantly increased above basal rates by CRH and/or AVP. The AP cells fr om immature fetuses responded significantly to CRH (406 +/- 16%), AVP (114 +/- 8%), and CRH plus AVP (559 +/- 38%), whereas cells from matur e fetuses responded only to AVP (249 +/- 40%) or to CRH plus AVP (570 +/- 146%). In AP cells from mature adrenalectomized fetuses, the respo nse pattern resembled that of immature intact fetal sheep (CRH, 429 +/ - 76%; AVP, 146 +/- 15%; CRH plus AVP, 541 +/- 94%). Neonatal AP cells responded to CRH (196 +/- 25%), AVP (442 +/- 71%), and CRH plus AVP ( 646 +/- 93%). Further characterization of IL cells (n = 6 fetal and 2 neonatal) indicated that they were inhibited by dopamine (basal ACTH s ecretion decreased by 25 +/- 4%; ACTH secretory response to CRH decrea sed by 32 +/- 10%). These results show that fetal neurointermediate lo be cells secrete irACTH under basal and stimulated conditions. Moreove r, the pattern of response of AP and neurointermediate lobe cells to s ecretagogues is influenced by gestational age and, possibly, cortisol.