Nitric oxide synthase and sex hormones

If you need more information on NOS and sexual function, visit the page on erections and skim over the page on limiting bottom growth.

Nitric Oxide Synthase and Bodily Functions

NOS (nitric oxide synthase) synthesizes nitric oxide (NO) and L-citrulline from L-arginine (and oxygen).

There are three different NOS isoforms, which are found throughout the body and have different uses in it. Some functions of note are for cardiovascular health, immune system response, and neurotransmission— in short, NOS and NO are important compounds!

The three different isoforms are:

— eNOS/NOS 3 (in endothelial/blood vessel tissue)

— iNOS/NOS 2 (in immune cells, largely undetectable unless you are sick)

— nNOS/NOS 1 (mostly in the brain and neurons)

eNOS and nNOS activate at a certain calcium threshold (100nM), while iNOS is calcium independent and essentially always active. iNOS is also independent of cellular location. (http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=253)

Malfunctions in NOS have been linked to cancer, diabetes (when NO spreads across all of an organ), and heart disease (due to lack of NO and NO synthase). (https://sites.google.com/a/udel.edu/nitricoxidesynthase/project-definition)

NOS and Sex Hormones

Estrogen:

• Upregulates eNOS
• Upregulates nNOS in the brain
• Increases LH (at least in rats without ovaries)
• Estrogen receptor beta could have a direct link to the actions and increase of eNOS. (http://circres.ahajournals.org/content/85/11/979)
• NO activity (regulated by estrogen) moderates bone deposition, primarily driven by iNOS and estrogen’s effects on it. (https://www.rndsystems.com/resources/articles/estrogen-immune-system-mice-and-women-and-nitric-oxide)
• Decreases muscle relaxation in vaginal tissue.

Androgens:

• DHT is tied to a higher increase in nNOS compared to testosterone. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC16298/)
• DHT appears to be a major factor in more nNOS activity in the brain. (https://academic.oup.com/endo/article/138/8/3093/2987423)
• Lower T (more precisely, DHT) levels seem to correspond with lowered levels of nNOS in nitregeric/MPG neurons. (https://academic.oup.com/endo/article/138/8/3093/2987423)
• Essentially, penile (and very likely clitoral) function appears to be almost completely androgen dependent. Despite this, blocking androgen appears to drastically decrease NOS activity as opposed to content. (https://academic.oup.com/biolreprod/article-abstract/55/3/567/2760492)

General:

• nNOS and eNOS are found in clitoral and penis tissue and both have to do with erections, mainly as they help control levels of cGMP (cyclic GMP) and lead to changes in the corpus cavernosum that cause erection.
• NOS/nNOS is not the only factor controlling erection! There’s another pathway that can activate cGMP as well, though NOS is still needed.
• More NOS production may decrease the amount of NO produced by other isoforms of NOS. iNOS is especially strong in this regard. http://circres.ahajournals.org/content/85/11/979)
• All forms of NOS possess NAPH-D activity, and other isoforms besides nNOS can be found in neurons.
• nNOS expression is present in nitregeric/MPG neurons of the brain, where they likely control urogenital function. (https://academic.oup.com/endo/article/138/8/3093/2987423)
• NO levels in the brain (mostly spurred by nNOS) control processes such as neurotransmission and GnRH levels. nNOS is located near GnRH terminals in the brain. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC16298/)