Maybe too much GABA is being inhibited?, though as the study points out, results may vary. Personally, I believe serotonin should be stimulated (more) during daytime hours while GABA and growth hormone at night.
(01-06-2015, 06:20 PM)Lotus Wrote: allopregnanolone (ALLO) and Tetrahidroteoxicorticosterone (THDOC) (allosteric modulators) of GABA-A receptors.
The way finasteride causes post finasteride syndrome in certain individuals is unknown. Finasteride blocks the conversion of testosterone to dihydrotestosterone (DHT), but also causes changes in testosterone levels, LH and FSH.
Finasteride also blocks the biosynthesis of various neuro steroids such as allopregnanolone (ALLO) and Tetrahidroteoxicorticosterone (THDOC), which are isoforms of the enzyme 5 alpha reductase. ALLO and THDOC are positive modulators (allosteric modulators) of GABA-A receptors, which have the same mechanism of action of anxiolytic drugs such as benzodiazepines.
Finasteride has been shown to inhibit the biosynthesis of these neuro steroids, which can be one of the causes for the emotional and sexual symptoms reported. However, some symptoms, such as muscle wasting, loss of body hair and the continuation of symptoms long after the medication has been discontinued, have not been explained yet. Because some patients with SPF have normal or high levels of testosterone - but at the same time a complete clinical state of hypogonadism - it has been hypothesized that these individuals have developed a form of resistance to androgen hormones.
Characterization of brain neurons that express enzymes mediating neurosteroid biosynthesis.
Abstract
Allopregnanolone (ALLO) and tetrahydrodeoxycorticosterone (THDOC) are potent positive allosteric modulators of GABA action at GABA(A) receptors. ALLO and THDOC are synthesized in the brain from progesterone or deoxycorticosterone, respectively, by the sequential action of two enzymes: 5alpha-reductase (5alpha-R) type I and 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD). This study evaluates 5alpha-R type I and 3alpha-HSD mRNA expression level in mouse brain by using in situ hybridization combined with glutamic acid decarboxylase 67/65, vesicular glutamate transporter 2, glial fibrillary acidic protein, and S100beta immunohistochemistry. We demonstrate that 5alpha-R type I and 3alpha-HSD colocalize in cortical, hippocampal, and olfactory bulb glutamatergic principal neurons and in some output neurons of the amygdala and thalamus. Neither 5alpha-R type I nor 3alpha-HSD mRNAs are expressed in S100beta- or glial fibrillary acidic protein-positive glial cells. Using glutamic acid decarboxylase 67/65 antibodies to mark GABAergic neurons, we failed to detect 5alpha-R type I and 3alpha-HSD in cortical and hippocampal GABAergic interneurons. However, 5alpha-R type I and 3alpha-HSD are significantly expressed in principal GABAergic output neurons, such as striatal medium spiny, reticular thalamic nucleus, and cerebellar Purkinje neurons. A similar distribution and cellular location of neurosteroidogenic enzymes was observed in rat brain.
Taken together, these data suggest that ALLO and THDOC, which can be synthesized in principal output neurons, modulate GABA action at GABA(A) receptors, either with an autocrine or a paracrine mechanism or by reaching GABA(A) receptor intracellular sites through lateral membrane diffusion.