Chronic administration of neuropeptide Y into the lateral ventricle inhibits both the pituitary-testicular axis and growth hormone and insulin-like growth factor I secretion in intact adult male rats

Abstract

Neuropeptide Y (NPY) is known to be involved in the central regulation of appetite, sexual behavior, and reproductive function. Whereas central administration of NPY strongly stimulates feeding in satiated animals, diet restriction or other unfavorable metabolic situations, such as diabetes, produce enhanced NPY gene expression and NPY release in the hypothalamus. Numerous studies have indicated that acute central administration of NPY results in various actions on LH secretion in the rat, either stimulatory or inhibitory. We recently demonstrated that chronic infusion of NPY into the lateral ventricle of adult intact female rats profoundly inhibited both the gonadotropic and somatotropic axes, with disruption of estrous cyclicity. Furthermore, we showed that central chronic infusion of NPY delayed sexual maturation in female rats. To analyze the effects of the same type of chronic NPY treatment on the pituitary-testicular axis, 45-day-old Sprague-Dawley male rats were implanted with stainless steel cannulas in the right lateral ventricle. Ten days later, Alzet osmotic minipumps were filled with different NPY solutions, adjusted to deliver 6, 18, or 36 micrograms/day, connected to the intracerebroventricular (icv) cannula, and sc implanted dorsally. The effects of these treatments were evaluated over 7 days. In one case, rats were castrated 5 days after initiation of NPY treatment, and the effect of castration was evaluated 2 days later. Chronic icv infusion of NPY produced the expected dose-related increases in food intake from 33.0 +/- 0.9 (basal) to 53.4 +/- 3.3 g/day (18 micrograms NPY/day) and body weight gain (5.7 +/- 0.7 to 10.5 +/- 1.2 d/day). As in female rats, this orexigenic action of NPY resulted in a significant dose-related decrease in pituitary weight, from 12.4 +/- 0.7 to 9.9 +/- 0.4 mg. The 7-day NPY infusion produced highly significant decreases in seminal vesicle weight (853 +/- 77 to 230 +/- 31 mg) and testis weight (3.82 +/- 0.09 to 3.18 +/- 0.15 g; P = 0.003). Plasma levels of testosterone (231 +/- 71 to 48 +/- 13 ng/dl), LH (20.7 +/- 3.7 to 9.1 +/- 1.2 ng/ml), and FSH (282 +/- 17 to 190 +/- 18 ng/ml) were markedly decreased at the 18 micrograms/day dosage, as also demonstrated for the 36 micrograms/day dosage. None of these effects was observed if vehicle was infused into the lateral ventricle instead of the NPY solution. When bilateral orchidectomy was performed 5 days after initiation of the NPY infusion (18 micrograms/day), the immediate LH and FSH rises usually seen after castration were seriously blunted.(ABSTRACT TRUNCATED AT 400 WORDS)

Inhibitory effects of central neuropeptide Y on the somatotropic and gonadotropic axes in male rats are independent of adrenal hormones

“…This is in keeping with findings that acute administration of glucocorticoids stimulate basal and growth hormone releasing hormone--induced GH secretion, and reduce the potency of IGF--1 mediated negative feedback [38]. Central NPY is known to inhibit several parameters of the somatotropic axis in rats [4,22,25], most probably via stimulation of somatostatin secretion from neurons in the periventricular nucleus [22]. Since adrenalectomy and central NPY administration have additive inhibitory effects on plasma IGF--1 levels, these interventions probably inhibit the somatotropic axis via divergent pathways.…”

“…The obesity syndrome which results from chronically elevated hypothalamic NPY levels in rodents [3,28,30,33,40,46,47] is still present even when NPY--induced hyperphagia is prevented [3,30,46], demonstrating that hyperphagia is not necessary for central NPY to produce its obesity--like effects. NPY in the hypothalamus is also involved in the regulation of several other important physiological processes including growth [4,22,25], reproduction [4,5,25], and fluid balance [13]. For example, intracerebroventricular (ICV) administration of NPY to rats has been shown to inhibit the somatotropic axis by reducing the pituitary content of growth hormone (GH) [4], abolishing the normal pulsate release of GH into the plasma [25], and consequently reducing the plasma concentrations of GH and its main effector in the periphery insulin--like growth factor I (IGF--1) [4,22,25].…”

“…NPY in the hypothalamus is also involved in the regulation of several other important physiological processes including growth [4,22,25], reproduction [4,5,25], and fluid balance [13]. For example, intracerebroventricular (ICV) administration of NPY to rats has been shown to inhibit the somatotropic axis by reducing the pituitary content of growth hormone (GH) [4], abolishing the normal pulsate release of GH into the plasma [25], and consequently reducing the plasma concentrations of GH and its main effector in the periphery insulin--like growth factor I (IGF--1) [4,22,25]. Centrally infused NPY was also shown to inhibit several parameters of the gonadotropic axis of both male and female intact rats, such as the reduction of plasma sex hormone levels, resulting in reduced gonadal weight and impaired sexual function [4,5,25].…”

“…For example, intracerebroventricular (ICV) administration of NPY to rats has been shown to inhibit the somatotropic axis by reducing the pituitary content of growth hormone (GH) [4], abolishing the normal pulsate release of GH into the plasma [25], and consequently reducing the plasma concentrations of GH and its main effector in the periphery insulin--like growth factor I (IGF--1) [4,22,25]. Centrally infused NPY was also shown to inhibit several parameters of the gonadotropic axis of both male and female intact rats, such as the reduction of plasma sex hormone levels, resulting in reduced gonadal weight and impaired sexual function [4,5,25]. The diverse roles of NPY are mediated by several different Y--receptor subtypes, five of which have been cloned to date (Y1, Y2, Y4, Y5 and Y6).…”

Distinct endocrine effects of chronic haloperidol or risperidone administration in male rats

“…altered hepatic glycogen or lipid storage significantly affect liver weight). Testis and seminal vesicle were weighed as an index of activity of the hypothalamo-pituitary-gonadotropic axis, which not only significantly affects the weight of these tissues (Pierroz et al, 1996) but also affects body composition (Mudali and Dobs, 2004).…”