Hypothalamic-pituitary-gonadal (HPG) axis function fundamentally affects the physiology of eating. We review sex differences in the physiological and pathophysiological controls of amounts eaten in rats, mice, monkeys, and humans. These controls result from interactions among genetic effects, organizational effects of reproductive hormones (i.e., permanent early developmental effects), and activational effects of these hormones (i.e., effects dependent on hormone levels). Male-female sex differences in the physiology of eating involve both organizational and activational effects of androgens and estrogens. An activational effect of estrogens decreases eating 1) during the periovulatory period of the ovarian cycle in rats, mice, monkeys, and women and 2) tonically between puberty and reproductive senescence or ovariectomy in rats and monkeys, sometimes in mice, and possibly in women. Estrogens acting on estrogen receptor-α (ERα) in the caudal medial nucleus of the solitary tract appear to mediate these effects in rats. Androgens, prolactin, and other reproductive hormones also affect eating in rats. Sex differences in eating are mediated by alterations in orosensory capacity and hedonics, gastric mechanoreception, ghrelin, CCK, glucagon-like peptide-1 (GLP-1), glucagon, insulin, amylin, apolipoprotein A-IV, fatty-acid oxidation, and leptin. The control of eating by central neurochemical signaling via serotonin, MSH, neuropeptide Y, Agouti-related peptide (AgRP), melanin-concentrating hormone, and dopamine is modulated by HPG function. Finally, sex differences in the physiology of eating may contribute to human obesity, anorexia nervosa, and binge eating. The variety and physiological importance of what has been learned so far warrant intensifying basic, translational, and clinical research on sex differences in eating.

https://www.physiology.org/doi/pdf/10.1152/ajpregu.00446.2012

Sex differences in the physiology of eating

Exposure to restraint and brief intermittent tailshocks facilitates associative learning of the classical conditioned eyeblink response in male rats. Based on evidence of sex differences in learning and responses to stressful events, we investigated sexually dimorphic effects of a stressor of restraint and intermittent tailshock on classical eyeblink conditioning 24 h after stressor cessation. Our results indicate that exposure to the acute stressor had diametrically opposed effects on the rate of acquisition of the conditioned response in male vs. female rats. Exposure to the stressor facilitated acquisition of the conditioned response in males, whereas exposure to the same stressful event dramatically impaired acquisition in females. We further demonstrate that the stress-induced impairment in female conditioning is dependent on the presence of ovarian hormones. Conditioning of stressed sham-ovariectomized females was significantly impaired relative to the unstressed controls, whereas conditioning in stressed ovariectomized females was not impaired. We present additional evidence that estrogen mediates the stress-induced impairment in female acquisition. Females administered sesame oil vehicle and then stressed were significantly impaired relative to their unstressed controls, whereas females administered the estrogen antagonist tamoxifen prior to stress were not impaired. In summary, these results indicate that exposure to the same aversive event can induce opposite behavioral responses in males vs. females. These effects underscore sex differences in associative learning and emotional responding, and implicate estrogen in the underlying neuronal mechanism.

http://njc.rockefeller.edu/PDF_BN08/topic%203-shors-wood4066.pdf

Stress Facilitates Classical Conditioning in Males, but Impairs Classical Conditioning in Females through Activational Effects of Ovarian Hormones

The hypothalamic-pituitary-adrenal (HPA) axis is a major component of the systems that respond to stress, by coordinating the neuroendocrine and autonomic responses. Tightly controlled regulation of HPA responses is critical for maintaining mental and physical health, as hyper- and hypo-activity have been linked to disease states. A long history of research has revealed sex differences in numerous components of the HPA stress system and its responses, which may partially form the basis for sex disparities in disease development. Despite this, many studies use male subjects exclusively, while fewer reports involve females or provide direct sex comparisons. The purpose of this article is to present sex comparisons in the functional and molecular aspects of the HPA axis, through various phases of activity, including basal, acute stress, and chronic stress conditions. The HPA axis in females initiates more rapidly and produces a greater output of stress hormones. This review focuses on the interactions between the gonadal hormone system and the HPA axis as the key mediators of these sex differences, whereby androgens increase and estrogens decrease HPA activity in adulthood. In addition to the effects of gonadal hormones on the adult response, morphological impacts of hormone exposure during development are also involved in mediating sex differences. Additional systems impinging on the HPA axis that contribute to sex differences include the monoamine neurotransmitters norepinephrine and serotonin. Diverse signals originating from the brain and periphery are integrated to determine the level of HPA axis activity, and these signals are, in many cases, sex-specific.

Sex Differences in the HPA Axis

Regulatory role of brain angiotensins in the control of physiological and behavioral responses.

Brain angiotensin receptor subtypes in the control of physiological and behavioral responses

Plasma samples were obtained throughout pregnancy and pseudopregnancy from Sprague-Dawley (SD) rats and during pregnancy from rats of the Munich Wistar (MW) strain. The concentrations of progesterone, oestradiol, prolactin, plasma renin activity (PRA), aldosterone and corticosterone were measured by radioimmunoassay to establish hormonal profiles in the two strains of rat. Circulating progesterone concentrations in both strains of rat were significantly higher during pregnancy than in virgin controls, except at term in the SD group. The hormonal pattern for pseudopregnancy was similar to that of the first half of pregnancy. Oestradiol concentrations were similar to, or lower than, those in virgin controls throughout pseudopregnancy and for the first 2 weeks of pregnancy in both strains of rat. Increased concentrations of steroid were seen only in the pregnant groups towards term. In SD rats, highest prolactin concentrations were apparent during the first half of pregnancy and pseudopregnancy, and at term in the pregnant group. Pregnant MW rats showed a different profile for this hormone, with low levels throughout pregnancy except at term. In all groups PRA rose to a peak at day 9 and decreased to day 16. Pregnant SD rats also showed a significant increase at term. Aldosterone concentrations were significantly increased at several stages of pregnancy in both strains of rat, particularly during the second half of gestation. Pseudopregnant animals showed a different hormone profile, with no significant changes until day 16 when lower concentrations were recorded. There was little variation in the circulating corticosterone concentration except in pregnant rats at term when levels fell. These findings are discussed in relation to the known renal changes of pregnancy and pseudopregnancy.

Hormone profiles for progesterone, oestradiol, prolactin, plasma renin activity, aldosterone and corticosterone during pregnancy and pseudopregnancy in two strains of rat: correlation with renal studies.

J. C. Atherton

Papers

Hormone profiles for progesterone, oestradiol, prolactin, plasma renin activity, aldosterone and corticosterone during pregnancy and pseudopregnancy in two strains of rat: correlation with renal studies.