Re: Calling out the low SHBG guys
Hi,
Let me interrupt you, I'm also the one with low SHBG levels and I may have some insights
Based on my latest research (and personal experiments) I 'm starting to draw some initial conclusions, that maybe there is indeed no direct casual link between low SHBG and problems with testosterone and TRP.
However I think that SHGB and TT/FT may correlate (strongly?) due another factors like COMT polymorphism (mutations), adrenal glands, and someway ATP production in mitochondria.
My thesis aren't based on tones of research in scientific facility, but more on analytical thinking and experimentation of the simple guy. I may be wrong but I would like to share my ideas. Maybe this can help or steer someone on the right track.
Some recent research indicates that COMT variations are involved with levels of prolactin and estrogen metabolism.
I will draw the hypothesis that due some type COMT alleles activity and consequent constantly lower levers of dopamine - > higher levels of prolactin are present. Higher prolactin level can cause lower shbg levels and weakened testosterone production / retention. High prolactin will also mess with estrogen and so on...
Above case is hard to be overcome with TRT, because external, additional testosterone will initially raise dopamine, but this increase will be defeated by constant COMT (over)activity. This is just vicious cycle...
There are also a few, another, additional complications, correlations and physiological connections, which I'm currently trying to understand...
Therefore currently I suggest that the main aim for SHBG lovers
is to control and keep healthy dopamine levels and the same counts for dopamine / norepinephrine ratio.
Because dopamine levels are dependent on many factors, for example adrenal gland conditions, testosterone and estrogen levels, mitochondrial processes etc. it is hard to find one silver bullet to cure them all
Currently I'm researching on: CoQ10, ALCAR, Omega-3, green tea, acetylocholine and L-theanine which all looks promising.
If new ideas arise I will try to share them again.
Below some research as a start base:
Estrogen Deficient Male Mice Develop Compulsive Behavior
Rachel A. Hill
,
Kerry J. McInnes
,
Emily C.H. Gong
,
Margaret E.E. Jones
,
Evan R. Simpson
,
Wah Chin Boonemail address
Received 17 August 2005; received in revised form 20 January 2006; accepted 22 January 2006. published online 27 March 2006.
Abstract
Full Text
PDF
Images
References
Background
Aromatase converts androgen to estrogen. Thus, the aromatase knockout (ArKO) mouse is estrogen deficient. We investigated the compulsive behaviors of these animals and the protein levels of catechol–O–methyltransferase (COMT) in frontal cortex, hypothalamus and liver.
Methods
Grooming was analyzed during the 20-min period immediately following a water-mist spray. Running wheel activity over two consecutive nights and barbering were analyzed. COMT protein levels were measured by Western analysis.
Results
Six-month old male but not female ArKO mice develop compulsive behaviors such as excessive barbering, grooming and wheel-running. Excessive activities were reversed by 3 weeks of 17?-estradiol replacement. Interestingly, the presentation of compulsive behaviors is accompanied by concomitant decreases (p < .05) in hypothalamic COMT protein levels in male ArKO mice. These values returned to normal upon 17?-estradiol treatment. In contrast, hepatic and frontal cortex COMT levels were not affected by the estrogen status, indicating region- and tissue-specific regulation of COMT levels by estrogen. No differences in COMT levels were detectable between female animals of both genotypes.
Conclusions
This study describes the novel observation of a possible link between estrogen, COMT and development of compulsive behaviors in male animals which may have therapeutic implications in obsessive compulsive disorder (OCD) patients.
Biochem J. 1996 Dec 1;320 ( Pt 2):499-504.
Role of P2-purinergic receptors in rat Leydig cell steroidogenesis.
Foresta C, Rossato M, Nogara A, Gottardello F, Bordon P, Di Virgilio F.
Source
Università di Padova, Italy.
Abstract
The present study investigated the effects of extracellular ATP on the intracellular calcium ion concentration ([Ca2+]i) and testosterone production in isolated adult rat Leydig cells. This nucleotide caused an increase in [Ca2+]i, with a maximal effect at a concentration of 100 microM ATP, comprising a rapid initial spike followed by a long-lasting plateau. The first rapid spike was dependent on the release of Ca2+ from internal stores, since it also occurred in Ca(2+)-free medium and was abolished after depletion of internal stores with thapsigargin. The second, long-lasting, phase was dependent on the influx of Ca2+ from the extracellular medium. After 3 h of incubation, extracellular ATP stimulated testosterone secretion in a dose-dependent manner, with a maximal effect at 100 microM. Activation of steroidogenesis by ATP was fully dependent on the presence of Ca2+ in the external medium. Among different nucleotides, only ATP, adenosine 5'-[gamma-thio]triphosphate, UTP, benzoylbenzoic-ATP and 2-methylthio-ATP were effective in inducing both the rise in [Ca2+]i and testosterone secretion. These effects were blocked by preincubation of Leydig cells with oxidized ATP, an inhibitor of the P2Z-purinergic receptor subtype. These results show that rat Leydig cells possess P2-purinergic receptors whose activation triggers an increase in [Ca2+]i due to the release of Ca2+ from internal stores and Ca2+ influx from the external medium. The stimulatory effect of extracellular ATP on testosterone secretion seems to be coupled to the influx of Ca2+ from the external medium.
Catechol-O-methyl transferase - Wikipedia, the free encyclopedia
"The [COMT] Val158Met polymorphism
A functional single-nucleotide polymorphism (a common normal variant) of the gene for catechol-O-methyltransferase results in a valine to methionine mutation at position 158 (Val158Met) rs4680.[12] The Val variant catabolizes dopamine at up to four times the rate of its methionine counterpart.[13] However, the Met variant is overexpressed in the brain,[14] resulting in a 40% decrease in functional enzyme activity.[15] The lower rates of catabolisis for the Met allele results in higher synaptic dopamine levels following neurotransmitter release, ultimately increasing dopaminergic stimulation of the post-synaptic neuron. Given the preferential role of COMT in prefrontal dopamine degradation, the Val158Met polymorphism is thought to exert its effects on cognition by modulating dopamine signaling in the frontal lobes."
Molecular genetics support Gray’s personality
theory: the interaction of COMT and DRD2
polymorphisms predicts the behavioural
approach system
Martin Reuter1, Anja Schmitz1, Philip Corr2 and Juergen Hennig1
1 Centre of Psychobiology and Behavioral Medicine, Department of Psychology, University of Giessen, Germany
2 Department of Psychology, University of Wales Swansea, Swansea, UK
Abstract
The present study provides the first direct molecular genetics support for Gray’s Reinforcement
Sensitivity Theory (RST), which is one of the most influential biologically oriented personality theories. It
was investigated whether the DRD2 TaqIA and the COMT polymorphisms were related to the dimensions
of Gray’s personality theory, as measured by the Carver and White BIS/BAS scales. In a sample of 295
healthy subjects results revealed significant DRD2rCOMT interactions (i.e. epistasis) for the total BAS
scale (related to positive emotionality) and for the subscales Drive (D) and Fun Seeking (FS). High BAS
scores were observed if the catabolic enzyme activity and the D2 receptor density as indicated by the
two polymorphisms were in disequilibrium, i.e. in the presence of the Valx/A1x (low enzyme activity/
high receptor density) or the Val+/A1+ (high enzyme activity/low receptor density) alleles. In a random
subsample (n=48), it could be demonstrated that those allele combinations of COMT and DRD2
associated with high BAS scores also had significantly lower prolactin levels under resting conditions,
indicating high dopamine activity, compared to those allele combinations with low BAS scores. Furthermore,
two-way interactions of DRD2 TaqIArsmoking status and of the Met allele of COMTrsmoking
status on FS and Metrgender on BIS could be shown.
Received 23 January 2005; Reviewed 3 March 2005; Revised 7 March 2005; Accepted 14 March 2005
)]
