NEUROKININ-A LEVELS IN THE HYPOTHALAMUS OF RATS AND MICE - EFFECTS OF CASTRATION, GONADAL-STEROIDS AND EXPRESSION OF HETEROLOGOUS GROWTH-HORMONE GENES

Neurokinin A is a decapeptide with pharmacological activities and localizations similar to those of substance P. In this report we describe the effects of castration and administration of testosterone, dihydrotestosterone and estradiol, on neurokinin A levels in the hypothalamus of male rats. The effects of estradiol and testosterone on hypothalamic neurokinin A were also examined in normal mice and in transgenic mice carrying the genes for human or bovine growth hormone (hGH, bGH, respectively). Either acute or prolonged castration was followed by a decrease of neurokinin A concentrations in the hypothalamus of male rats. The substitutive administration of testosterone propionate or estradiol benzoate for 14 days resulted in an increase of hypothalamic neurokinin A levels above the values found in intact animals. A lower dose of testosterone propionate or dihydrotestosterone also increased hypothalamic neurokinin A levels in the hypothalamus of castrated rats. In normal intact male mice a single injection of estradiol benzoate significantly increased hypothalamic neurokinin A levels. A similar effect was observed in transgenic mice carrying the bGH gene with phosphoenolpyruvate carboxykinase (PEPCK) promoter, while mice carrying the hGH gene failed to show any response to estradiol. In castrated male mice, either normal or transgenic, carrying the bGH gene with metallothionein promoter, a single injection of testosterone propionate significantly increased neurokinin A levels in the hypothalamus. It is concluded that sex steroids may regulate the levels of neurokinin A in the hypothalamus of rats and mice. © 1990.