Effects of bromocriptine on pituitary and adrenal cortex in pre-adrenarchal rabbits
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The effect of bromocriptine on the morphological picture and steroid content of the adrenal gland, and on certain pro-opiomelanocortin (C) peptides in the pituitary gland was evaluated in preadrenarchal rabbits. Eighteen immature male rabbits (5 weeks of age), were treated for 10 days with saline (n = 10, 2 ml sc) or bromocriptine mesylate (n = 8, 3 mg/kg sc) two times/day. After the last administration all animals received dexamethasone (0.25 mg im) and the next morning, 60 min after ACTH injection (0.25 mg im), plasma was drawn and they were sacrificed. Adrenals and pituitaries were immediately removed. For each animal, one adrenal gland was fixed, dehydrated and embedded in paraffin for histology; the other one was stored in saline for determination of androstenedione (A), dehydroepiandrosterone (DHA), 17-OH progesterone (17 P), and cortisol. Steroids were analyzed by RIA after previous extraction and celite-ethyleneglycol cromatography, or directly (cortisol). The immunoreactivities (ir) related to beta-Endorphin (B-EP), ACTH and alpha-MSH were evaluated in pituitary homogenates using speficic RIAs. The bromocriptine-treated rabbits showed a significant increase in the percentage of the adrenal zona reticularis (21.5 ± 3.9% of total cortex vs. 12.7 ± 1.3% in controls, p< 0.05, mean ± SE), and a decrease of the zona fasciculata (57.6 ± 3.13% vs. 67.7 ± 2.05% in controls, p < 0.05). No significant changes were observed in the relative percentage of the zona glomerulosa. While, after ACTH stimulation, the adrenal content of cortisol, 17 P and A was similar in both groups of animals, the A/17 P ratio, was significantly (p < 0.05) higher in treated (0.19 ± 0.02) than in control rabbits (0.10 ± 0.01). Given that the apparent efficiency of the combined activities of 11 beta and 21 hydroxylase appears to be the same in both groups (ratio cortisol × 103/17 P: 33.5 ± 5.7 vs 39.3 ± 6.5 in controls), bromocriptine-treated rabbits showed a clear predominance of androgenic over glucocorticoid responses, as demonstrated by the significant (p< 0.01 ) less ratio cortisol × 103/A in these animals (137.2 ±27.6) than in controls (318 ± 41.4). Bromocriptine-treated rabbits also showed significantly greater pituitary content of both ir alpha-MSH (2.01 ±0.47 pmol/mg) and ir B-EP (20.1 ± 4.0 fmol/mg) than controls (0.94 ± 0.23 pmol/mg, alpha-MSH, p < 0.05; 6.9 ± 1.96 fmol/mg, B-EP, p < 0.01). The pituitary ir ACTH was similar in both groups. In conclusion, these results indicate that bromocriptine treatment during the preadrenarchal period in rabbits: a) Induces the growth of the adrenal zona reticularis, which is accompanied by the increase of 17–20 desmolase activity, and b) Increases the pituitary content of alpha-MSH and B-EP ir. Taken together, these facts seem to indicate that adrenarche could occur as à phenomenon related to alpha-MSH and/or other factor(s) subject to dopaminergic control, but independent of ACTH.
Key-wordsBromocriptine rabbit adrenarche zona reticularis POMC dopamine
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