Review of the Y chromosome, Sry and hypertension

Abstract

The following review examines the role of the SHR Y chromosome and specifically the Sry gene complex in hypertension and potential mechanisms that involve the sympathetic nervous system and renin angiotensin system. There are consistent gender differences in hypertension, with a greater proportion of males affected than females in most mammalian populations. Our earlier studies demonstrated that a portion of the gender differences in blood pressure (BP) in the SHR rat mapped to the SHR Y chromosome. In rats, males with the SHR Y chromosome have higher BP than females, or males with a different Y chromosome. Consistent with these results, several human population studies have confirmed a Y chromosome effect on BP. Our more recent studies focus on a transcription factor, Sry, as the locus involved in not only BP modulation but effects on other phenotypes. The Sry locus is an evolutionarily conserved locus on the mammalian Y chromosome responsible for testis determination and is a transcription factor. The Sry locus contains a highly conserved High Mobility Group (HMG) box region responsible for DNA binding. Mutations in the HMG box result in sex reversal. We have found multiple functional copies of Sry in SHR and WKY male rats. There is abundant evidence that testes determination may not be Sry’s only function as it is expressed in the brain, kidney and adrenal gland of adult males. These findings have potential implications for gender physiology research which involve, the sympathetic nervous system, renin angiotensin system, androgen receptor regulation and prostate physiology.

Sex Hormones and Sex Chromosomes Cause Sex Differences in the Development of Cardiovascular Diseases

“…For example, Sry is expressed in the brain and other tissues, especially in catecholaminergic cells and neurons, where its effects may include effects on hypertension. 11–13 Studies of XY mice with different versions of the Y chromosome show remarkable differences in the severity of autoimmune disease. 14 Effects of the Y chromosome must be specific to males, but the implied sex difference could be compensated for by other factors in females.…”

Biological factors underlying sex differences in neurological disorders

“…Alternatively, a regulatory mutation in human SRY gene or a SRY binding site mutation in its target gene may also increase the risk of males in developing these brain disorders. Indeed, SRY polymorphism was shown to be responsible for the hypertensive component of male SHRs (Ely et al, 2010;Turner et al, 2009), which have higher blood pressure compare to the female SHRs. Since SHRs are also a rat model of ADHD (Russell, 2002;Sagvolden et al, 2005), it would be of interest to determine whether manipulating SRY expression can alter ADHD-like symptoms in the SHRs.…”

Allogeneic Liver Transplantation and Subsequent Syngeneic Hepatocyte Transplantation in a Rat Model: Proof of Concept for in vivo Tissue Engineering

“…Quantitative (q)PCR was performed to determine the amount of transplanted male cells in the female recipient livers using the sex-determining region of the Y-chromosome (SRY) as a quantification marker [Ely et al, 2010]. QIAamp DNA FFPE tissue kits (Qiagen, Hilden, Germany) were used to isolate genomic (g)DNA from formalin-fixed and paraffin-embedded liver sections.…”