Dwight M. Nance

Sexual behavior and neural degeneration following hypothalamic knife cuts

Frontal (FC), frontal lateral (FLC) or sham deafferentations were performed on adult ovariectomized (OVX) female rats. Cuts were produced retrochiasmatically with a modified Halasz knife equipped with an extrudable blade (1.5 mm radius). At 60 days after surgery each animal was tested for lordosis behavior (LQ) following either 3 daily injections of estradiol benzoate (EB) alone or with progesterone (P). Male sex behavior was tested 5 times at 4 day intervals during a 21 day regime of daily treatment with testosterone propionate. Additional FC and FLC rats were sacrificed at 10 and 14 days after surgery and degeneration patterns were studied using the Fink-Heimer method. Brains were removed and prepared for histological examination of cut location and dimensions in each rat. Behavioral effects of knife cuts were analyzed by 2 methods: (1) grouping based on common areas of glial scars; (2) a multiple regression analysis of cut morphometrics with sex behavior. No group differences were found when LQ of FC and FLC rats were compared with Sham animals after EB alone. The expected increase in LQ which follows EB and P treatment was not observed in FLC rats when means were compared. In male sex behavior tests FC and FLC groups showed more total mounts than Sham rats, however, the differences were not statistically significant. Multiple regression analysis of individual cut location and width with behavior indicated that more anterior and lateral the cut location (FC and FLC) the greater the decrement in female sex behavior. Fink-Heimer studies revealed that both FC and FLC cuts produced degeneration bilaterally in the stria medullares, habenula, fasciculus retroflexus, in addition to arcuate, ventromedial and periventricular hypothalamic nuclei. FLC cuts also resulted in bilateral degeneration in the zona incerta, the cerebral peduncles and in the medial forebrain bundle. Collectively these data indicate the complete interruption of anterior and lateral connections of the anterior hypothalamic area and mediobasal hypothalamus with the remainder of the brain in the female rat reduced lordosis behavior.

Sexual dimorphism in the regulation of caloric intake and body weight of rats fed different diets.

Abstract Female, androgenized female (AF), and male rats were given access to 1 of 3 diets—chow (C), high-dextrose (D-chow:dextrose, 2:1), and high-fat (F-chow:Crisco, 2:1) for 2 months. Caloric intake (CI), water intake, and body weights were monitored daily. Responses to gonadectomy and a single injection of estradiol benzoate (EB) were also studied. For females, F- and C-fed rats had comparable CIs, whereas D-fed rats chronically ate much less. For males, F-fed rats overate, whereas C- and D-fed rats had comparable CIs. The pattern of CI of AF rats fed the 3 diets was intermediate between that of males and females. Male rats were less responsive to the anorexic effects of EB than were the other two groups, and the F-diet potentiated the anorexic effects of EB in all three groups. Results are discussed in terms of a sex difference in the hypothalamic regulation of feeding behavior which is modulated by gonadal hormones.

Estrogen modification of feeding behavior in the female rat: Influence of metabolic state

Abstract The effects of estrogen on feeding behavior and body weight regulation of adult ovariectomized rats were observed after 48 hr of food deprivation. The depletion of body nutrient stores caused by food deprivation resulted in an attenuation of the effects of estrogen treatment on food intake, eating time, meal size, meal duration and the number of meals. Nevertheless, estrogen treatment in fasted animals did shorten the interval between meals immediately after access to food was restored. Indices of the satiating effects of individual meals and the deprivation effects of intervals between meals were calculated for selected times. These indices also indicated an influence of estrogen even in the fasted condition. Estrogen diminished the satiety produced by the first meal after food access was restored, while the deprivation effects of the interval between the first and second meals were enhanced. During the dark period on the first day of refeeding, the satiating effects of food remained reduced in the fasted condition, and estrogen did not appear to further affect satiety compared to oil treatment, but estrogen did lower the deprivation effects of intermeal intervals compared to oil treatment. Estrogen treatment in non-fasted animals lowered both satiety and deprivation effects during the dark period. The varying influence of estrogen on the deprivation effects of intermeal intervals suggests that the influence of estrogen depends upon the long-term effects of an animals metabolic state.

Changes in estrogen and progestin receptor binding resulting from retrochiasmatic knife cuts

Retrochiasmatic frontolateral knife cuts (FLC) or sham operations (Sham) were performed with a Halasz-type knife. All animals were primed with estrogen plus 0.5 mg progesterone (P) and tested for lordosis both before and after surgery. Two weeks after the last test they received estradiol (E2) in Silastic capsules and were sacrificed 2 days later for determination of either nuclear estrogen receptors or cytosol progestin receptor binding in brain and pituitary (PIT). Rats which had received FLC showed significantly lower lordosis quotients relative to Shams, and relative to their own pre-surgery scores. Nuclear E2-receptor binding was significantly reduced in the hypothalamus (HYPO) following FLC, but not in preoptic area (POA) or PIT. No changes in cytosol P-receptor binding were observed in HYPO, POA or PIT following FLC. Our results suggest a positive correlation between the number of hypothalamic E2-receptors and the capacity to display lordosis, and emphasize the importance of anterolateral connections to the HYPO for the progesterone-induced facilitation of lordosis.

Experiments with a reported anorexigenic tripeptide: PyroGluHisGlyOH ☆

A newly described tripeptide, pyro-Glu-His-Gly-OH, which was reported to produce profound and long-term anorexia and weight loss in female mice, was initially tested in female rats. After total dose of either 8, 16, or 32 microgram SC of the peptide, administered across an eight day interval, there was no detectable effect on food intake, body weight, or estrous cycles of female rats. In a second study, we attempted to verify the anorexigenic potency of this peptide in mice. Total doses of 3.4 and 6.8 microgram, injected across a 20 day period, had no effect on the food intake or body weight of S/W albino female mice. Thus, the anorexigenic potency of pyro-Glu-His-Gly-OH has yet to be established.

Effects of diet upon hypothalamic vulnerability to goldthioglucose in male mice

Three groups of male mice were fed three different diets for about 3 weeks: powdered chow (C), a high fat (F) diet (chow:Crisco, 2:1), and a high dextrose (D) diet (chow:dextrose, 2:1). Food and water intake and body weights (BWts) were measured daily. On Day 20 of the study, mice were injected IP with 0.3 mg/g of goldthioglucose (GTG). Two days later, the mice were sacrificed and brains were removed for histological examination of GTG-induced lesions in the ventromedial hypothalamus (VMH). It was found that (1) F-fed mice ate more and gained more BWt than C- and D-fed mice, and (2) the average GTG lesion volume of F-fed mice was twice as large as those of C- and D-fed mice. In view of known alterations in sensitivity of the VMH to goldthioglucose with changes in glucose metabolism, it is suggested that the larger goldthioglucose induced lesions in F-fed mice may be due to elevated blood levels of goldthioglucose or altered glucose metabolism in goldthioglucose sensitivity cells in the VMH.

Effects of estrogen upon hypothalamic vulnerability to goldthioglucose in mice

Two groups of ovariectomized albino mice were given subcutaneous injections of either seasame oil or increasing doses of estradiol benzoate (EB) for 8 days. Mice were housed in groups of three; food intake (FI) and body weight (Bwt) were measured daily during this period. After 8 days, all mice were injected IP with 0.3 mg/g of goldthioglucose (GTG) and sacrificed 2 days later. The extent of hypothalamic damage after GTG was assessed histologically. Although EB did not depress FI or Bwt, perhaps because of some behavioral interaction within the groups of mice, the extent of hypothalamic damage after GTG was significnatly increased in EB-treated mice relative to that of oil-injected controls. These data support the view that estrogen may enhance the uptake and/or storage of glucose by the ventromedial hypothalamus.

Similar effects of estrogen and lateral hypothalamic lesions on feeding behavior of female rats

Many similarities exist between the inhibitory influence of estrogen on food intake (FI) and body weight (BWt) in female rats and the effect of lateral hypothalamic (LH) lesions on energy balance. Thus, a possible interaction of small electrolytic LH lesions (0.8 mA/10 sec) with hormone-dependent changes in FI, BWt and feeding patterns of female rats was examined. Relative to sham operated controls, rats with LH lesions showed a transitory period of anorexia and initial loss of BWt. Subsequently, FI and BWt gains of lesioned rats returned to control levels although a small chronic reduction in mean BWt was observed relative to sham animals. Daily changes in FI and BWt during 4-day estrous cycles as well as post-ovariectomy increases in FI and BWt were comparable for lesion and sham animals. Also, both groups showed a similar decrease in FI and BWt following a SC injection of estradiol benzoate (EB). Possible effects of LH lesions were further examined by analyzing feeding patterns. Feeding behavior was continuously monitored with photodetectors and recorded on an Esterline Angus event marker before and after a single SC injection of 6 micrograms of EB. Relative to shams, LH animals showed an exaggerated diurnal distribution of meals, ate smaller meals of shorter duration and had larger intervals between meals during the light period. EB was found to shift the feeding patterns of sham animals towards the meal patterns shown by the lesioned rats (exaggerated diurnal distribution of meals, etc.). However, the lesioned rats also showed a normal change in feeding patterns following EB, albeit these changes occurred from a markedly different baseline level.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of estrogen upon feeding inhibition produced by intragastric glucose loads

Abstract Two studies were performed to determine if estrogen could potentiate the inhibitory effects of glucose on feeding behavior. In the first experiment, ovariectomized rats were injected with either 6 μg of estradiol benzoate (EB) or with sesame oil, and two days later were given 5 ml intragastric loads of either 40% glucose or 13.5% urea by gavage. Gavage was performed after a 12-hr fast, during the light period. Food intake (FI) was measured at hourly intervals, starting 2 hr after gavage and reaccess to food as well as daily throughout the experiment. In a second experiment, rats received a similar treatment, except that gavage was performed in an unfasted condition, during the dark period. It was found that (1) a 12-hr fast abolishes anorexic effects of EB, but leaves the inhibitory effects of glucose intact, (2) EB does not potentiate short-term effects of glucose, and (3) EB enhances delayed (22 hr after gavage) effects of glucose upon feeding. These findings are consistent with the hypothesis that EB modified the long-term control of feeding behavior, probably at the level of the ventromedial hypothalamus.

Nocturnal feeding pattern in the prepubertal rat: influence of the ventromedial hypothalamus (VMH)

Abstract Daily feeding patterns, food intake and changes in body weight of male and female prepubertal rats were observed across a period from 21 to 50 days of age. Light/dark differences in feeding were found for both males and females throughout the recorded period, with feeding occurring predominantly during the dark period. The light/dark difference in feeding behavior gradually increased as the animals developed. Bilateral lesions placed in the VMH of female rats at 21 days of age disrupted the light/dark differences in feeding behavior primarily by decreasing dark period feeding. These lesions further resulted in a period of hypophagia and retarded body weight gain as well as a delay in pubertal onset. These data indicate that prepubertal rats regulate their feeding behavior so that food intake occurs principally during the dark period and that the integrity of the VMH is necessary for this regulation.