Women with cystic fibrosis are at increased risk for mucoid conversion of Pseudomonas aeruginosa, which contributes to a sexual dichotomy in disease severity.

A higher incidence of colorectal cancer (CRC) is found in males compared to females. Young women (18–44 years) with CRC have a better survival outcome compared to men of the same age or compared to older women (over 50 years), indicating a global incidence of sexual dimorphism in CRC rates and survival. This suggests a protective role for the sex steroid hormone estrogen in CRC development. Key proliferative pathways in CRC tumorigenesis exhibit sexual dimorphism, which confer better survival in females through estrogen regulated genes and cell signaling. Estrogen regulates the activity of a class of Kv channels (KCNQ1:KCNE3), which control fundamental ion transport functions of the colon and epithelial mesenchymal transition through bi-directional interactions with the Wnt/β-catenin signalling pathway. Estrogen also modulates CRC proliferative responses in hypoxiaviathe novel membrane estrogen receptor GPER and HIF1A and VEGF signaling. Here we critically review recent clinical and molecular insights into sexual dimorphism of CRC biology modulated by the tumor microenvironment, estrogen, Wnt/β-catenin signalling, ion channels, and X-linked genes.

Membrane-localized estrogen receptor can alter metabolism without translocating to the nucleus.

Anion conductance across theDrosophila melanogaster Malpighian (renal) tubule was investigated by a combination of physiological and transgenic techniques. Patch-clamp recordings identified clusters of 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS)-sensitive “maxi-chloride” channels in a small domain of the apical membrane. Fluid secretion assays demonstrated sensitivity to the chloride channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid, diphenylamine-2-carboxylate, anthracene-9-carboxylic acid, and niflumic acid. Electrophysiological analysis showed that the calcium-mediated increase in anion conductance was blocked by the same agents. Vibrating probe analysis revealed a small number of current density hot spots, coincident with “stellate” cells, that were abolished by low-chloride saline or the same chloride channel blockers.GAL-4-targeted expression of an aequorin transgene revealed that the neurohormone leucokinin elicits a rapid increase in intracellular calcium levels in stellate cells that precedes the fastest demonstrable physiological effect. Taken together, these data show that leucokinins act on stellate cells through intracellular calcium to increase transcellular chloride conductance through channels. As electrogenic cation conductance is confined to principal cells, the two pathways are spatially segregated in this tissue.

There is increasing interest in sexual and gender dimorphism in disease. We reviewed the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) carriage and bloodstream infection (BSI), which shows a male predominance, and explored some of the possible reasons. Males are more prone to bacterial sepsis, but some studies suggest females may have a poorer prognosis from BSI. Hand-hygiene behavior varies according to gender. Males are less compliant, which in turn may predispose them to higher colonization and infection rates. Female hormones such as estrogen affect the expression of virulence factors in Pseudomonas aeruginosa, and although not studied, this may also apply to S. aureus. Further research is required on the relationship between gender and risk of infection, the reasons for higher MRSA carriage and BSI rates in males, the value of gender-specific infection prevention campaigns, and other factors such as the possible role of contact sports and occupation.