Influence of gender and endogenous sex steroids on catecholaminergic structures involved in physiological adaptation to hypoxia

Abstract

Mechanisms underlying sex-related differences in adaptation to high altitude were investigated by assessing the turnover of dopamine and noradrenaline in structures of the chemoafferent pathway, i.e. carotid body and brainstem noradrenergic cell groups (A1, A5, A6, A2 to which chemosensory fibres project). The influence of gender was assessed in male and female rats reared at an altitude of 3600 m, whereas the influence of endogenous sex hormones was evaluated by castration. Haematocrit, red blood cell count and plasma erythropoietin levels were lower in females than in males (-5%, -15%, -53%, respectively). Dopamine and noradrenaline turnover were higher in female structures (carotid body: +51%; A2: +140%; A1: +54%; A5: +27%). Dopamine and noradrenaline turnover in carotid body and brainstem cell groups were differently affected by castration, i. e. enhanced by orchidectomy (carotid body: +134%; A2: +120%; A1: +69%; A5: +67%) but inhibited by ovariectomy (carotid body: -33%; A2: -92%). Orchidectomy elicited a reduction in haematocrit (-10%), haemoglobin concentration (-8%) and red blood cell count (-24%), whereas haematological status remained unaltered after ovariectomy. Therefore, both gender and endogenous sex steroids may control catecholamine activity differently in structures involved in the chemoafferent pathway, thus providing a neurochemical basis for sex-related differences in adaptation to hypoxia.

Sex Differences in Blood Pressure Response to Intermittent Hypoxia in Rats

“…The adverse effects of exposure to continuous hypoxia are less dramatic in females than males, [12][13][14][15] and sex steroids reduce many of these adverse effects. 14 Within the central nervous system, gender and sex hormones have been shown to alter neuronal responses to hypoxia in cardiovascular-related areas, 16,17 particularly in catecholaminergic structures involved in the chemoreflex pathway. 16 Such alterations could contribute to sex-related differences in the response to hypoxia.…”

“…14 Within the central nervous system, gender and sex hormones have been shown to alter neuronal responses to hypoxia in cardiovascular-related areas, 16,17 particularly in catecholaminergic structures involved in the chemoreflex pathway. 16 Such alterations could contribute to sex-related differences in the response to hypoxia. Mean arterial pressure (MAP), heart rate (HR), and activity in ovariectomized (OVX) female rats (nϭ6) before (C1 to C7), during (H1 to H7) and after (R1 to R7) exposure to intermittent hypoxia (IH).…”

Gender Comparisons of Control of Breathing and Metabolism in Conscious Mice Exposed to Cold

“…These results suggest that cold acts centrally to modulate the ventilatory pattern of female and male mice differently. Gender differences in central modulation of breathing have been reported in several brain regions such as the paraventricular nucleus and arcuate nucleus of the hypothalamus, the caudal portion of the nucleus tractus solitarius, locus coeruleus, and the A5 portion of the ventral lateral pons [13, 14, 29]. Moreover, other regions involved in modulation of metabolic rate such as the paraventricular nucleus of the hypothalamus are also involved in control of breathing [30].…”

“…In the CNS, short periods of cold also increase serotonin and norepinephrine levels in the hypothalamus of rodents [13, 25]. …”

“…In addition, classic signs of chronic mountain sickness occur almost exclusively in adult male subjects [10]. At a cellular level, gender-specific differences in ventilatory responses to hypoxia or hypercapnia may be due to variations in neurotransmitter receptor levels, sex steroid hormone receptor levels in various brain regions associated with regulation of ventilation and metabolism independent of sex steroid hormone levels [11, 12, 13, 14]. …”