EFFECTS OF HYPOPHYSECTOMY ON GALANINERGIC NEURONS IN THE RAT HYPOTHALAMUS

To understand better the relationship between hypothalamic galaninergi c neurons and the pituitary gland, we studied the effects of hypophyse ctomy on hypothalamic galanin (GAL) content and distribution by radioi mmunoassay and immunohistochemistry, and on GAL mRNA by Northern blot analysis. Three weeks after hypophysectomy, performed at 5 or 8 weeks of age, the hypothalamic concentrations of GAL and GAL mRNA were reduc ed by 30-50% in both male and female rats, compared to age- and sex-ma tched controls. Similar reverse-phase HPLC retention times of hypothal amic GAL were observed in intact and hypophysectomized rats. The reduc tion of hypothalamic GAL concentration following hypophysectomy was ti me-dependent, as peptide levels were unaffected one week after surgery . Immunohistochemistry showed regional differences in the effect of hy pophysectomy on galaninergic neurons. In the hypophysiotropic hypothal amus, the scarce GAL immunoreactivity normally observed in the arcuate nuclei was no longer detectable in hypophysectomized rats, and the in tense GAL immunoreactivity of the external zone of the median eminence progressively decreased and completely disappeared 3 and 6 weeks afte r hypophysectomy. In contrast, in the neurohypophyseal system, there w as an increase of GAL labelling of the perikarya and emerging axons in the supraoptic and lateral-paraventricular nuclei, 1 and 3 weeks afte r hypophysectomy, that disappeared 6 weeks after hypophysectomy. An in crease of GAL immunoreactivity was also observed in the internal zone of the median eminence 1 week but not 3 weeks after hypophysectomy. We conclude that hypophysectomy reduces the content of GAL and GAL mRNA in the rat hypothalamus. These changes are time-dependent and clearly detected after 3 weeks. The neurohypophyseal and hypophysiotropic gala ninergic systems respond differently to hypophysectomy. In the neurohy ophyseal system, the transient increase of GAL immunoreactivity could be related to axonal injury, diabetes insipidus or decreased neurosect ion. In contrast, the marked decrease of the GAL immunoreactivity foun d in the hypophysiotropic system, mainly in the external zone of the m edian eminence, accounts for the overall changes in hypothalamic pepti de content and likely results from the loss of feedback up-regulation by pituitary or pituitary-dependent factors.