Testosterone Regulation of Renal α _2B -Adrenergic Receptor mRNA Levels

Abstract

Androgens regulate blood pressure and renal alpha 2-adrenergic receptors in a parallel fashion in the spontaneously hypertensive rat (SHR). The present studies investigated whether this regulation of renal alpha 2B-adrenergic receptors occurs at the mRNA level. Male and female SHR were gonadectomized at 4 weeks of age. The gonadectomized rats were implanted with or without testosterone propionate. Sham-gonadectomized rats served as controls. Total kidney RNA was purified, and alpha 2B-adrenergic receptor mRNA was quantified with a reverse transcriptase-polymerase chain reaction (RT-PCR) assay. The assay uses a mimic RNA added at known concentrations to the sample RNA. The mimic was constructed from the target sequence in the alpha 2B-adrenergic receptor mRNA plus a 20-bp insertion of a random nucleotide sequence. The amount of alpha 2B-adrenergic receptor mRNA present in each sample was obtained by determining the equivalence point between the amount of RT-PCR product formed in the target band versus the mimic band, which were resolved by gel electrophoresis. Intact males had more than two times as much alpha 2B-adrenergic receptor mRNA as intact females. Castration of males reduced the male-female difference by more than 60%. Ovariectomy slightly increased the alpha 2B-adrenergic receptor mRNA level compared with that of intact females. Treatment with testosterone elevated alpha 2B-adrenergic receptor mRNA levels of gonadectomized males and females to the level of intact males. The alpha 2B-adrenergic receptor mRNA levels correlated remarkably well with renal alpha 2-adrenergic receptor density. We conclude that testosterone regulates renal alpha 2B-adrenergic receptor gene expression at the mRNA level in the SHR.

Cardiovascular and metabolic phenotypes in relation to the ADRA2B insertion/deletion polymorphism in a Chinese population

“…Although the precise mechanism underlying the male-female differences remains to be elucidated, sex hormones are probably involved. Indeed, testosterone stimulates the expression of a2B-adrenoceptors in spontaneously hypertensive rats [27] and is required for full expression of the receptor in salt-induced hypertension in male Sabra rats [28].…”

Modulation of aortic vascular reactivity by sex hormones in a male rat model of metabolic syndrome

“…Also androgens may aid the onset of hypertension in spontaneously hypertensive rats, through the increased activity of the tyrosinehydroxylase enzyme (Kumai et al, 1995), which primarily increases the levels of norepinephrine (NE) in the blood. Gong et al (1995) found that androgens can regulate the blood pressure in spontaneously hypertensive rats, and showed that the treatment with testosterone (T) elevates the number of α 2 -adrenergic receptors in the whole kidney of females and in castrated males, compared with controls.…”

Testosterone Dependence of Salt-Induced Hypertension in Sabra Rats and Role of Renal α2-Adrenoceptor Subtypes

“…In addition, ␣ 2B -adrenoceptor densities were markedly increased by the high salt diet. These high levels, which appear to be the consequence of an overexpression of the encoding gene, have also been observed in SHR rats (Gong et al, 1994(Gong et al, , 1995. However, the ␣ 2A -adrenoceptor mRNA was clearly present in kidneys of intact SBH rats under both normal and high salt diet.…”

“…In the kidney of the normotensive rat, ␣ 2A -and ␣ 2B -adrenoceptor subtypes have been characterized by binding studies (Uhlen and Wikberg, 1991). In SHR rats, testosterone regulates renal ␣ 2B -adrenoceptor density at the mRNA level (Gong et al, 1995). From this study, it has been postulated that the effects of testosterone on renal ␣ 2B -adrenoceptor mRNA and ␣ 2B -adrenoceptor density are tightly associated with blood pressure and probably responsible for the hypertension in SHR rats.…”