Aging and the hypothalamo-pituitary-testicular axis in the rat

Several experiments have been performed in order to clarify the mechanisms through which aging in male rats brings about profound modifications of the neuroendocrine system (reduced pulsatile secretion of LH and FSH, decreased serum levels of gonadotropins and testosterone, etc.). (1) It has been found that the number of mu opioid receptors decreases significantly in the hypothalami of old male rats; the substitution therapy with testosterone is ineffective in increasing the number of mu opioid receptors. These data suggest that the decrease of hypothalamic mu opioid receptors is not due to a decline of serum testosterone levels, but appears to be an independent phenomenon. (2) K opioid receptors increase significantly in the amygdala and in the thalamus of old male rats. These results show that aging, in addition to mu receptors, affects also the number of K receptors in selected areas of the brain. The increase of the number of K receptors in the amygdala might have some bearing on the decrease of serum gonadotropins observed in aged rats, since the amygdala is involved in the nervous circuitry influencing the hypothalamo-pituitary-gonadal axis. (3) The study of the release of LHRH from the hypothalamus of old male rats with an in vitro perfusion system shows that the release of the hormone is comparable in young and old animals, both in basal and in K+ stimulated conditions. These results indicate that the hypothalamus of old male rats retains the capacity of releasing LHRH both in basal and in stimulated conditions. (4) It has been observed that the number of LHRH receptors at the level of the anterior pituitary is significantly reduced in old male rats. This finding might explain the low serum levels of gonadotropins and testosterone in aged rats, due to a lack of an adequate response of the pituitary to hypothalamic LHRH.