Chronic intracerebroventricular (icv) administration of neuropeptide-Y (NPY; 10 fig/day) was performed in normal female rats to investigate its hormonal and metabolic consequences. Intracerebroventricular NPY produced hyperphagia, increased basal insulinemia, as well as liver and adipose tissue lipogenic activity. It also increased basal morning corticosteronemia. When NPY-induced hyperphagia was prevented by pair-feeding, the icv NPY treatment resulted in the same increases in basal insulinemia and corticosteronemia, and liver and white adipose tissue lipogenesis was still higher than that in respective controls. Under the ad libitum and pair-feeding conditions, icv NPY stimulated glucose uptake as well as total lipoprotein lipase activity in white adipose tissue; it resulted in an increased total activity of hepatic and white adipose tissue acetyl coenzyme-A-carboxylase. As all hormonal and metabolic changes elicited by icv NPY remained present (at the same or to a lesser extent depending upon the parameter considered) when hyperphagia was prevented by pair-feeding, it was, thus, shown that icv NPY per se induces peripheral hormonal and metabolic alterations via efferent routes, which remain to be determined. The effects of icv NPY reported in this study are similar to the defects observed in the early phase of genetic obesity in rodents, the hypothalamus of which has increased NPY levels. NPY could, thus, be of relevance in the occurrence of genetically induced obesity. (Endocri

Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity

Glucocortcoids mediate the stress-induced extracellular accumulation of glutamate ☆

https://www.jbc.org/content/271/3/1764.full.pdf

Expression of the peroxisome proliferator-activated receptor alpha gene is stimulated by stress and follows a diurnal rhythm.

The product of the ob gene, leptin, is a hormone secreted by adipose tissue that acts in the hypothalamus to regulate the size of the body fat depot. Its central administration has been shown to decrease food intake and body weight, while favoring energy dissipation. As glucocorticoids are known to play a permissive role in the establishment and maintenance of obesity syndromes in rodents, it was hypothesized that they do so by restraining the effect of leptin. Leptin injected intracerebroventricularly as a bolus of 3 μg in normal rats induced modest reductions in body weight and food intake. In marked contrast, the same dose of leptin had very potent and long-lasting effects in decreasing both body weight and food intake when administered to adrenalectomized rats. Further, glucocorticoid supplementation of adrenalectomized rats dose-dependently inhibited these potent effects of leptin. These data suggest that glucocorticoids play a key inhibitory role in the action of leptin. Under normal conditions, this inhibitory influence of glucocorticoids may prevent lasting hypophagia. In obesity with degrees of hypercorticism, it may contribute to “leptin resistance,” whose etiology is still little understood.

https://diabetes.diabetesjournals.org/content/diabetes/46/4/717.full.pdf

Glucocorticoids as Counterregulatory Hormones of Leptin: Toward an Understanding of Leptin Resistance

The neonatal rat shows a period of decreased responsiveness to noxious stimuli during the first 3 weeks of life, but the nature of this impairment is still controversial. To test the functionality of the hypothalamus-pituitary-adrenal axis during this period, we studied pituitary and adrenal responsiveness to exogenous ovine CRF and the ability of various stressors (ether vapors, electroshocks, and hypoxia) to elicit ACTH and corticosterone secretion. We also measured hypothalamic CRF content and pituitary ACTH content as well as CRF-binding sites in the anterior pituitary. From days 3–10, small elevations in plasma ACTH and corticosterone levels were observed after a 3-min exposure to ether vapors or electroshocks. In contrast, during this period, a 20- min exposure to hypoxia (5% O2 in N2) was unable to trigger measurable ACTH secretion, while corticosterone was significantly elevated. From days 14–21, plasma ACTH and corticosterone levels increased significantly after exposure to ether stress, hypoxia,...

Ontogeny of the stress response in the rat: role of the pituitary and the hypothalamus.

A radioimmunoassay for corticosterone was developed and characterized using corticosterone antiserum (377, Niswende) and a simple ethanol extraction procedure. The antiserum appeared to be highly specific fo corticosterone. Intraassay variability was 3.67 +- 0.75% (mean +- SE) at 50 pg of corticosterone; interassay variability with a mean value of 51.15 pg was 6.98 +- 1.01%. Assay sensitivity was 9.48 +- 0.60 pg. Utilizing this assay, serum obtained from adrenalectomized and adrenalectomized-ovariectomized rats yielded lower corticosterone values than serum from intact or ovariectomized rats. Intact females had lower corticosterone values than intact males. Rats exposed to elevated temperature (32.5/sup 0/) displayed significantly (P < 0.001) elevated plasma corticosterone levels (48.48 +- 4.37 ..mu..g/100 ml) compared to control (24.5/sup 0/) animals (21.31 +- 2.02 ..mu..g/100 ml). The high specificity, sensitivity, precision, recovery level, and ease of this technique make it useful for the study of either serum or plasma corticosterone.

Radioimmunoassay (RIA) of serum corticosterone in rats.

SummaryAmplitude of pulsatile release of LH was examined in OVX rats of ages 3-4, 9-11, and 17-18, months, serially bled via chronic jugular catheters. At the time of ovariectomy, rats showed normally cycling (NC), irregularly cycling (IC), or constant estrus (CE) ovarian activity. Amplitude of pulsatile release of LH was significantly reduced in CE rats as compared to all other groups. Further, LH pulse amplitude appeared to be more closely associated with reproductive state at the time of ovariectomy than with the age of the animal. Thus, LH pulse amplitude was greatest in NC rats, intermediate in IC rats, and lowest in CE rats, regardless of age. These data suggest that a common, central mechanism may be responsible for both the changes in reproductive pattern and the changes in pulsatile release of LH which accompany aging in the rat.

C. L. Chen

Papers

Radioimmunoassay (RIA) of serum corticosterone in rats.

Alteration in pulsatile release of LH in aging female rats.

Altered hypothalamic dopamine depletion rate and LHRH content in noncyclic hamsters.