1.
Effect of menstrual cycle and female hormones on TRP and TREK channels in modifying thermosensitivity and physiological functions in women.
Uchida, Y, Izumizaki, M
Journal of thermal biology. 2021;:103029
Abstract
Thermoregulation is crucial for human survival at various ambient temperatures. Transient receptor potential (TRP) and TWIK-related K+ (TREK) channels expressed in sensory neurons play a role in peripheral thermosensitivity for temperature detection. In addition, these channels have various physiological roles in the skeletal, nervous, immune, vascular, digestive, and urinary systems. In women, the female hormones estradiol (E2) and progesterone (P4), which fluctuate during the menstrual cycle, affect various physiological functions, such as thermoregulation in hot and cold environments. The present review describes the effect of female hormones on TRP and TREK channels and related physiological functions. The P4 decreased thermosensitivity via TRPV1. E2 facilitates temporomandibular joint disease (TRPV1), breast cancer (TRPM8), and calcium absorption in the digestive system (TRPV5 and TRPV6), inhibits the facilitation of vasoconstriction (TRPM3), nerve inflammation (TRPM4), sweetness sensitivity (TRPM5), and menstrual disorders (TRPC1), and prevents insulin resistance (TRPC5) via each channel. P4 inhibits vasoconstriction (TRPM3), sweetness sensitivity (TRPM5), ciliary motility in the lungs (TRPV4), menstrual disorder (TRPC1), and immunity (TRPC3), and facilitates breast cancer (TRPV6) via each channel as indicated. The effects of female hormones on TREK channels and physiological functions are still under investigation. In summary, female hormones influence physiological functions via some TRP channels; however, the literature is not comprehensive and future studies are needed, especially those related to thermoregulation in women.
2.
Effect of estrogen-active compounds on the expression of RACK1 and immunological implications.
Buoso, E, Masi, M, Galbiati, V, Maddalon, A, Iulini, M, Kenda, M, Sollner Dolenc, M, Marinovich, M, Racchi, M, Corsini, E
Archives of toxicology. 2020;(6):2081-2095
-
-
Free full text
-
Abstract
We previously demonstrated the existence of a balance among steroid hormones, i.e. glucocorticoids and androgens, in RACK1 (receptor for activated C kinase 1) expression and innate immunity activation, which may offer the opportunity to use RACK1 expression as marker to evaluate immunotoxicity of hormone-active substances. Because of the existence of close interconnections between the different steroid hormone receptors with overlapping ligand specificities and signaling pathways, in this study, we wanted to investigate a possible effect of estrogenic active compounds, namely 17β-estradiol, diethylstilbestrol, and zearalenone, on RACK-1 expression and innate immune responses using THP-1 cells as experimental model. All compounds increased RACK1 transcriptional activity as evaluated by reporter luciferase activity, mRNA expression as assessed by real time-PCR and protein expression by western blot analysis, which paralleled an increase in LPS-induced IL-8, TNF-α production, and CD86 expression, which we previously demonstrated to be dependent on RACK1/PKCβ activation. As the induction of RACK1 expression can be blocked by the antagonist G15, induced by the agonist G1 and by the non-cell permeable 17β-estradiol conjugated with BSA, a role of GPER (previously named GPR30) activation in estrogen-induced RACK1 expression could be demonstrated. In addition, a role of androgen receptor (AR) in RACK1 transcription was also demonstrated by the ability of flutamide, a nonsteroidal antiandrogen, to completely prevent diethylstilbestrol-induced RACK1 transcriptional activity and protein expression. Altogether, our data suggest that RACK1 may represent an interesting target of steroid-active compounds, and its evaluation may offer the opportunity to screen the immunotoxic potential of hormone-active substances.
3.
Cell surface estrogen receptors coupled to cNOS mediate immune and vascular tissue regulation: therapeutic implications.
Stefano, GB, Peter, D
Medical science monitor : international medical journal of experimental and clinical research. 2001;(5):1066-74
Abstract
The vast number of reports dealing with estrogen and its associated molecular signaling cascades deal with genomic processes. However, recently data is emerging that demonstrates that estrogen may also work via estrogen cell surface receptors. In this regard, we describe such receptors on human monocytes, granulocytes and vascular endothelial cells. It would appear that these receptors are coupled to constitutive nitric oxide synthase derived nitric oxide release via the stimulation of intracellular calcium transients. It is this cascade that has the ability to down regulate both immune and vascular cellular processes, i. e, adherence. Based on this, for example we surmise that in menopause an earlier initiation of estrogen therapy may be more beneficial so as to prevent a decrease in its cellular signaling and maintenance functions, at least with respect to NO-related events.