Different Roles for the Pituitary and Adrenal Cortex in the Control of Enkephalin Peptide Localization and Cortico-Medullary Interaction in the Sheep Adrenal during Development

Abstract

We have investigated the effect of adrenocorticotrophic hormone (ACTH) replacement after fetal hypophysectomy on the pattern of localization of enkephalin-containing peptides (enkephalins) and phenylethanolamine N-methyltransferase (PNMT) in the fetal sheep adrenal. We have also investigated the relative roles of the fetal pituitary and adrenal cortex in determining the extent of the interdigitation of the peripheral adrenaline (AD)-containing cells of the adrenal medulla with the inner zones of the adrenal cortex in the late gestation fetus. Fetal hypophysectomy (Hx; n = 12) or sham operations (n = 8) were performd at 109–118d. At 138 or 139d, ACTH (1–24) (10.5 µg/h) was infused intravenously for 72 h into 4 Hx fetuses (Hx + ACTH group). Saline was infused for 72 h into 4 Hx fetuses (Hx + Sal) and into 4 sham-operated fetal sheep (Intact + Sal). Fetal adrenal glands were collected at autopsy from 141/2d Intact + Sal, Hx + Sal and Hx + ACTH groups, from 4 intact fetal sheep at 145–147d gestation (145/7d Intact group) and 4 Hx fetal sheep at 147–164d gestation (147/64d Hx group). Adrenals were also collected from 4 newborn lambs at 10–12d afterbirth (10/12d Newborn group). Using the peroxidase-antiperoxidase immunocytochemical staining method, sections of adrenal glands (10–12 µm) from all groups were stained anti-PNMT. Sections of adrenal glands from the 141/2d groups were also stained separately with anti-dopamine-β-hydroxylase (anti-DβH) and anti-enkephalin (anti-ENK). Morphometric analyses were carried out on mid-glandular sections stained with anti-PNMT and an index of the interdigitation between the adrenal cortex and adrenal medulla was calculated (i.e. interdigitation index = the ratio of the perimeter of the adrenal medulla to the perimeter of a circle of the same area as the adrenal medulla). In the 141/2dHx + Sal and the 141/2dHx + ACTH groups, more central adrenomedullary cells were stained with anti-PNMT than in the intact group. In the 141/2d Intact + Sal group, staining with anti-ENK was observed in the peripheral rim of adrenal medulla cells which were adjacent to and interdigi-tated with the cells of the adrenal cortex. In the intact and Intact + SAL group, the intensity of staining with anti-ENK in the central noradrenaline (NA)-containing region was variable with many unstained cells present. In the 141/2d Hx + Sal and Hx + ACTH groups, however, staining for enkephalins was present throughout the entire adrenal medulla. The interdigitation index of the adrenal medulla and the adrenal cortex was significantly increased in the 10/ 12d Newborn (3.00 ± 0.07), 145/7d Intact (2.68 ± 0.07), and the 141/2d Hx + ACTH (2.62 ± 0.06) when compared to the 147/64d Hx (1.42 ± 0.03), 141/2d Intact + Sal (1.29 ± 0.02) and 141/2d Hx + Sal (1.15 ± 0.01) groups (p < 0.05). When the data were combined for all fetal and newborn lamb adrenals there was a positive correlation between the area of the adrenal cortex and the interdigitation index (r = 0.802; P < 0.001). In summary, we found that the pattern of localizatio...

The effect of fetal hypophysectomy with or without ACTH replacement on the molecular weight profile of enkephalin-containing peptides in the adrenal medulla of the fetal sheep

“…development of the adrenal gland in the sheep fetus at late gestation. In agreement with previous studies, our data clearly demonstrate that the increase in adrenocortical growth and the prepartum increase in fetal plasma cortisol concentrations are dependent upon the presence of an intact fetal pituitary in the sheep fetus in late gestation (Basset & Thorburn, 1969;Boshier, Holloway & Liggins, 1981 ;Robinson et al 1983;Mesiano et al 1987;Coulter, Young, Browne & McMillen, 1991). In the present study, ACTH infusion (at 250 pg/ 24 h for 72 h ) in the hypophysectomized fetal sheep stimulated an increase in the adrenal weight, adrenal protein and fetal plasma cortisol concentrations beyond the normal levels found in the intact fetus at this gestational age.…”

“…In the present study, ACTH infusion (at 250 pg/ 24 h for 72 h ) in the hypophysectomized fetal sheep stimulated an increase in the adrenal weight, adrenal protein and fetal plasma cortisol concentrations beyond the normal levels found in the intact fetus at this gestational age. We observed previously that the adrenocortical area of hypophysectomized fetuses with ACTH replacement at 141-142 days of gestation was the same as that in intact fetal sheep at 145-147 days of gestation (Coulter et al 1991) and these data suggest that the level of ACTH replacement in the hypophysectomized group has accelerated the normal pattern of growth of the prepartum adrenal gland.…”

Differential expression of VEGF receptors in adrenal atrophy induced by dexamethasone: a protective role of ACTH

“…Our results suggest that ACTH is the major regulator of these effects, since ACTH injections within 7 days restored plasma corticosterone level to control values. These results are in agreement with studies in the hypophysectomized fetal sheep, which showed that adrenal growth could be restored by in utero ACTH replacement therapy (6,8,24).…”

“…Glucocorticoid hormones are thought to exert negative feedback inhibition on hypothalamic-pituitary-adrenocortical axis activity at the pituitary, hypothalamic, and extrahypothalamic levels. This ultimately results in decreased synthesis and secretion of both corticotropin-releasing hormone (CRH) and other corticotropic secretagogues and in an inhibition of the production and secretion of ACTH (8,24). A rapid atrophy of the adrenal cortex and the reduction of its steroid machinery ensue.…”

Basic fibroblast growth factor expression is regulated by corticotropin in the human fetal adrenal: a model for adrenal growth regulation.

“…Although similar studies in the fetus have been more difficult, a role for ACTH in fetal adrenal development is indicated (6,7). Recent studies in the hypophysectomized fetal sheep have shown that adrenal cortical growth could be restored by in utero ACTH replacement therapy (8).…”