Sex Differences in Brain and Plasma β-Endorphin Content following Testosterone, Dihydrotestosterone and Estradiol Administration to Gonadectomized Rats

Abstract

Aims: The present study aims at evaluating the effect of a 2-week treatment with testosterone (T), dihydrotestosterone (DHT) and estradiol valerate (E₂V) on brain and plasma β-endorphin (β-END) concentrations in gonadectomized rats of both sexes. Methods: Eight groups of female and 8 groups of male Wistar rats were included. For each sex, 1 group of gonad-intact and 1 group of gonadectomized rats were employed as controls (placebo). The other groups received subcutaneous T at the doses of 10 and 100 μg/kg/day (female rats) or 1 and 5 mg/kg/day (male rats). Subcutaneous DHT was administered at the doses of 1, 10, 100 μg/kg/day (female rats) or 0.1, 1 and 5 mg/kg/day (male rats). E₂V was administered subcutaneously at 0.05 mg/kg/day. β-END levels were measured in different brain areas and plasma. Results: Ovariectomy (OVX) induced a significant decrease in β-END in all brain areas analyzed as well as in plasma. Orchidectomy (OCX) reduced opioid concentration in the hypothalamus, anterior pituitary and neurointermediate lobe. In OVX rats, T replacement as well as E₂V significantly increased β-END concentration in all brain areas and in plasma. In the OCX group, T and E₂V did not influence β-END concentrations in different hypothalamic areas. However, they produced a significant rise in β-END levels in the hypothalamus, neurointermediate lobe, anterior pituitary and plasma. Conversely, DHT replacement did not affect β-END levels at any dose administered, either in males or females. Conclusions: The sensitivity of the endogenous opiatergic system to T administration seems to be sex-related. This effect is particularly evident in the brains of female animals where this endogenous endorphin elicits a much greater response than it does in males that have undergone gonadal steroid depletion and subsequent T replacement.

Anabolic–androgenic steroid effects on nociception and morphine antinociception in male rats

“…Conversely, Hammer et al (1993) found that hormone-depleted rats experienced reduced proenkephalin mRNA expression in various brain structures, and this reduction was not reversed with administration of DHT. Pluchino et al (2009) also found that depletion of gonadal hormones decreased brain beta-endorphin levels, and T administration conversely increased beta-endorphin levels in various brain areas and in the plasma of gonadectomized rats. In contrast, DHT treatment—using a 5 mg/kg/day regimen similar to that used in the present study—failed to restore beta-endorphin levels.…”

Impact of sex on pain and opioid analgesia: a review

“…Indeed, electrical stimulation of the PAG induces a robust, opioid-dependent analgesia (Reynolds, 1969) that is attenuated by intra-PAG injection of the opioid receptor antagonist (−)-naloxone (Akil et al, 1976). Sex differences in pain sensitivity have been suggested to occur, in part, due to differences in endogenous opioid neurotransmission and in the circulation of steroid hormones (Micevych et al , 2003; LeResche et al, 2003; Smith et al, 2006; Pluchino et al 2009). Specifically, studies in rodents indicate significant sex differences in the anatomical and physiological characteristics of the PAG-RVM-spinal cord circuit.…”

Neurosteroid Influences on Sensitivity to Ethanol

“…Testosterone is particularly important in the development of male-specific maturation in rodents and primates (Gupta et al, 1975; Sato et al, 2008). Although present in adult females, the concentration of circulating testosterone is much greater in adult male rodents (e.g., Pluchino et al, 2009) and primates (e.g., Muller et al, 2011), in whom it is linked to aggressive and reproductive behavior (Sato et al, 2008). Stålenheim et al (1998) reported that testosterone was associated with aggressive and antisocial behavior, which were more prevalent in alcoholic men with a family history of alcoholism.…”