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Notes: To further investigate how sex steroids regulate galanin (GAL) in the rat pituitary and hypothalamus, we examined the effects of prepubertal gonadectomy (Gx) and long-term (9 weeks) replacement with estradiol (E2) or testosterone (T) on pituitary and hypothalamic GAL concentrations in Wistar rats (5–6/group). Sham-operated animals served as controls (CTR). Pituitary GAL concentration was markedly higher in random-cycling CTR-females than in CTR-males (1391 ± 247 vs 39 ± 5 pg/mg protein, P〈0.01) and decreased after Gx only in females (20 ± 3 pg/mg protein, P〈0.01). E2 strongly increased pituitary GAL in Gx-females and Gx-males (4470 ± 365 and 3853 ± 347 pg/mg protein, P〈0.01), whereas T had no effect. Inversely, hypothalamic GAL was higher in CTR males than in CTR females (5.4 ± 0.3 vs 4.0 ± 0.5 ng/mg protein, P〈0.05), and decreased significantly after gonadectomy in males (3.7 ± 0.2 ng/mg protein, P〈0.01). The only steroid treatment that significantly modified hypothalamic GAL in Gx animals was administration of E2 to females (5.7 ± 0.4 ng/mg protein, P〈0.01 vs non-treated Gx). We also studied in hypophysectomized (Hx) rats (8/group) the effects of sex steroids on hypothalamic GAL concentration and distribution. The low hypothalamic GAL concentration observed in male and female Hx rats (1.0 ± 0.1 ng/mg protein) was significantly increased by T in males and in females (respectively, by 40% and by 50%, P〈0.02) and by E2 in males (by 60%, P〈0.02). Immunohistochemistry showed that both E2 and T increased GAL labeling in fibers restricted to the lateral regions of the median eminence of male and female Hx rats, a distribution corresponding to that of GnRH-immunoreactive fibers. In conclusion, in addition to the marked stimulatory effect of estradiol on pituitary GAL, endogenous and exogenous sex steroids also modulate hypothalamic GAL in male and female rats. Both E2 and T may exert a stimulatory influence on hypothalamic GAL concentration and histochemical analysis shows that sex steroids enhance GAL immunoreactivity in a subset of neurons that closely overlaps the distribution of GnRH neurons.

Notes: Dietary zinc-deficiency induces a striking reduction and a cyclic pattern of food intake in rodents. To elucidate the mechanisms for these effects, we studied the hypothalamic content, synthesis, and distribution of galanin (GAL) and neuropeptide Y (NPY) during zinc deficiency and refeeding in the rat. In Wistar rats, three weeks of zinc-deprivation consistently induced a reduction and a cyclic pattern of night-and day-time food intake, as well as of water intake. This was accompanied in zinc-deficient (ZD) rats, and to a lesser extent in pair-fed (PF) rats, by a decrease of hypothalamic GAL mRNA concentration (CTR: 100±8, ZD: 61±4, PF: 78±2 arbitrary densitometric units, ADU, P〈0.01) and an increase of hypothalamic NPY (CTR: 100±11, ZD: 154±10, PF: 126±4 ADU, P〈0.05), without peptide modification. The two neuropeptidergic systems were not affected by the cycles of feeding, with the exception of the NPY-immunoreactivity in the suprachiasmatic nuclei (geniculo-hypothalamic tract), that was inversely correlated to the food intake in both ZD and PF animals. In a second experiment, we showed that zinc-repletion for 4 days suppressed the behaviour induced by a two-week zinc-deprivation, and reversed the increase of NPY mRNA in ZD animals. We finally demonstrated that zinc-deficiency induced a similar behaviour in Zucker rats. However, in these rats whose synthesis of NPY is constitutively up-regulated, no change of NPY synthesis was observed in ZD rats, suggesting that the increase observed in Wistar is adaptative rather than instrumental to the abnormal food intake. In conclusion, we have further characterized the cyclic feeding behaviour of the zinc-deficient Wistar rats, and shown in these animals a decreased activity of the GAL system and an increased activity of the NPY system, likely corresponding to a compensatory response of the two neuropeptidergic systems, as observed in food-deprived animals. As spontaneous food intake of ZD rats does not increase, a resistance to NPY could also be present. These behavioural and neuropeptidergic changes were partially reversed by reintroduction of zinc in the diet. In Zucker rats, the same behaviour occurred despite an insensitivity of the NPY system to the zinc-deficiency. In addition, we describe a nutritional regulation of the NPY-immunoreactivity in the geniculo-hypothalamic tract, that could constitute the substrate of circadian rhythm modulation by timed feeding.