Female mice exhibited higher kidney Olfr558 expression levels than male mice at 6 weeks of age (0.720 vs 0.473 AU; p=0.029), supporting a tissue-specific pattern during early postnatal development.
Absolute Event Rate: 0.72% vs 0.473%
p-value: p=0.029
Sex differences in blood pressure are well-established: during the reproductive years, females have blood pressure that is ~10mmHg less than that of males. Previously, we reported that an evolutionarily conserved G protein-coupled receptor, Olfactory receptor 558 (Olfr558), is required for sex differences in blood pressure (PMID: 38507492). We also found that Olfr558 is expressed in vascular smooth muscle cells, and, in renin positive juxtaglomerular granular cells of the kidney. Given that sex differences in blood pressure first appear during puberty, this study aimed to investigate changes in Olfr558 expression during early postnatal development. To investigate this, we collected tissues with the highest Olfr558 expression (heart, kidney, skeletal muscle, and brown adipose tissue) from both male and female mice. In all of these tissues, Olfr558 is found in vascular smooth muscle. Four developmental timepoints were selected for tissue collections: postnatal day 0 (P0), postnatal day 20 (P20, directly after ‘mini-puberty’), 6-weeks (around the time of puberty), and 10-weeks (sexually mature adults). Olfr558 mRNA expression levels were quantified using quantitative polymerase chain reaction (qPCR). The Ct values for each tissue were normalized to a reference gene which was stable across age/sex: TATA-Box Binding Protein (TBP, for kidney, skeletal muscle, and brown adipose tissue) or Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH, for heart). ΔCt values were normalized to P0 males for each tissue. The results revealed a tissue-specific expression pattern for Olfr558. In the kidney, Olfr558 expression levels increase from P0 to P20 then decrease from P20 to 6 weeks, in both males and females. Sex differences in kidney Olfr558 expression are not seen at P0 or P20 but emerge at 6-weeks, with females exhibiting higher Olfr558 expression levels than males (females: 0.720 AU +/- 0.021 N=7 males: 0.473 AU +/- 0.032, N=7 p=0.029). In the heart, a transient sex difference is seen only at the P20 timepoint, with females having lower expression than males (females: 0.777 AU +/- 0.047 N=7, males: 0.977 AU +/- 0.017 N=7 p=0.031). In skeletal muscle, sex differences were seen at P20 and 6 weeks, with males exhibiting higher Olfr558 expression than females (P20 females: 0.784 AU +/- 0.048 N=7, P20 males: 1.002 AU +/- 0.027 N=7, p=0.001; 6 wk females: 0.405 AU +/- 0.022 N=7, 6 wk males: 0.567 AU +/- 0.036, p=0.0066). Both sexes exhibited decreased expression in skeletal muscle by 10 weeks, and sex differences were no longer apparent at 10 weeks. No significant expression changes were noted in brown adipose tissue throughout early development for either sex. The results support a tissue-specific pattern of expression for Olfr558 during early postnatal development; notably, sex differences in Olfr558 expression emerge around the time of puberty in the kidney and are sustained thereafter. Future studies will further explore the role of Olfr558’s sibling receptor Olfactory receptor 78 (Olfr78) during early development and the implications of Olfr558 expression on renin-expressing cells during development. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Rodriguez et al. (2026) studied Blood pressure sex differences. Female sex vs. Male sex was evaluated on Kidney Olfr558 expression at 6-weeks (AU) (p=0.029). Female mice exhibited higher kidney Olfr558 expression levels than male mice at 6 weeks of age (0.720 vs 0.473 AU; p=0.029), supporting a tissue-specific pattern during early postnatal development.