Sexual Differentiation And Ageing – The Broken Hypothalamic-pituitary-gonadal Axis

Sexual Differentiation And Ageing – The Broken Hypothalamic-pituitary-gonadal Axis

Sexual differentiation becomes more fuzzier when we grow older and older.
Male sexual differentiation is gone when the androgen hormone receptors in the hypothalamus-pituitary androgen hormonal feedback control loop are degenerated or become insensitive. That is, the hypothalamic-pituitary-gonadal axis is broken. Under this condition, the pituitary LH hormone remains low when the testosterone level is low. If The hypothalamic-pituitary-gonadal axis is still active, the pituitary gland will overshoot LH release in response to low serum testosterone. As a result, men will experience the so-called male “menopause” (andropause) symptoms produced by excessive LH, such as anxiety, sweating, sleeping disorder, mood swing, hot flushes, and so on, like women do in the midlife. The simplest pharmaceutical solution for male and female menopause symptoms is to break/castrate the hypothalamic-pituitary-gonadal axis with SSRIs antidepressants, that is to degenerate or desensitize the sex hormone receptors (testosterone receptors for men, or estrogen receptors for women) in the hypothalamus-pituitary axis. Breaking the hypothalamic-pituitary-gonadal axis will disable the sex hormone feedback control loop in the hypothalamic-pituitary-gonadal axis, so that the pituitary gland won’t release excessive LH in an attempt to reactivate the testicular/ovarian function. Thus, SSRIs performs chemical castration of the hypothalamic-pituitary-gonadal axis. A good or bad idea?
Therefore, old men become femalized (grow the breasts and shrink the penis), and lose muscles, bone density and manhood. Old men will no longer have to worry about erection or penile enlargement!.

Ref: http://www.hindawi.com/journals/ije/2013/107869/

 

Female-testis

5-alpha DiHydroTestosterone (DHT) grows everything in the male body for the good, the bad, and the ugly

5-alpha DiHydroTestosterone (DHT) grows everything in the male body for the good, the bad, and the ugly. ( http://www.ajandrology.com/preprintarticle.asp?id=123664 )

( Source: http://en.wikipedia.org/wiki/File:Dihydrotestosterone-3D-balls.png )


(Source: http://upload.wikimedia.org/wikipedia/commons/1/13/Steroidogenesis.svg )

Man, DHT (Dihydrotestosterone) grows your penis during your puberty and maximizes your erectile size during age 20-30 when it reaches the peak level, but causes no problems for your prostate. When you get older and your DHT level starts to drop, you start to experience prostate enlargement, even cancer!
https://www.jstage.jst.go.jp/…/endocr…/24/1/24_1_41/_pdf
What is wrong? DHT grows everything, but why does your prostate cell become inflammatory and change itself to cancerous cell? Biological clock onset of cancerous genes? The clock is ticking if you carry the gene. Can you silence the gene (clock)?
Yes, reduce cellular prostaglandin E2 (PG-E2) release. PG-E2 activates stem cells (good or bad/cancerous) to multiplicate the cells and to grow the bone/brain. This is why you have growing pains.

Although Prostaglandin E2 starts your life by allowing a sperm to fertilize an egg (disabling the egg immunity), lets you get out of the uterus (uterine ripping for childbirth) and grows your body (stimulating your cell, brain, memory, and bone growth), it can end your life with infection, inflammation, fever, immune disorders and cancers. During your puberty, it lets you experience growing pains. After you pass puberty, you should reduce/adjust your cellular prostaglandin E2 release, so that it won’t activate cancerous DNA for you.

Prostaglandin E2 can be induced by mechanical stretching of muscles, tissues or bones. For example, stretching boned promotes bone growth via prostaglandin E2. This principle has been used for manhood enlargement exercises or stretching. Over-stretching tissues (including erectile tissues and smooth muscles) generally stimulate the collagen protein release for tissues scaring. The tissue scarring can extended to compress the nerves and blood vessels in addition to stretching induced nerve and blood vessel damage or scarring. You should avoid mechanically stretching damage of the nerves, tissues and blood vessels, upregulate your DHT and 5-alpha reductase receptors in your erectile tissues, increase your hGH production to activate the penile somatic stem cells, boost the release of beta endorphin, and activate the genes cytokeratin 16 and transformation growth factor beta-3 for enbryonic scar-free healing and cellular growth (http://www.actionlove.com/cases/case11311.htm )!
http://jn.physiology.org/content/early/2010/10/27/jn.00730.2010.full.pdf+html ,
http://www.ncbi.nlm.nih.gov/pubmed/11311513 ,
http://www.ncbi.nlm.nih.gov/pubmed/9626402 ,
http://www.ncbi.nlm.nih.gov/pubmed/8666581 , and

http://www.researchgate.net/publication/14249866_In_situ_microdialysis_in_bone_tissue._Stimulation_of_prostaglandin_E2_release_by_weight-bearing_mechanical_loading )

Stress neurohormones norepinephrine and epinephrine can induce prostaglandin E2 release via stimulation of α1- and α2-noradrenergic receptors.
“Preoptic α1- and α2-noradrenergic agonists induce, respectively, PGE2-independent and PGE2-dependent hyperthermic responses in guinea pigs. ”
Carlos Feleder , Vit Perlik , Clark M. Blatteis, American Journal of Physiology – Regulatory, Integrative and Comparative PhysiologyPublished 1 June 2004Vol. 286no. R1156-R1166DOI: 10.1152/ajpregu.00486.2003
http://ajpregu.physiology.org/content/286/6/R1156
“Effect of norepinephrine and renal denervation on renal PGE2 and kallikrein in rats.”
Diz DI, Baer PG, Nasjletti A. Am J Physiol. 1981 Nov;241(5):F477-81.
http://www.ncbi.nlm.nih.gov/pubmed/6946712
“Increased renal secretion of norepinephrine and prostaglandin E2 during sodium depletion in the dog.” J A Oliver, J Pinto, R R Sciacca and P J Cannon, J Clin Invest. 1980;66(4):748–756. doi:10.1172/JCI109912.
http://www.jci.org/articles/view/109912/pdf
“Physiological concentrations of melatonin inhibit the norepinephrine-induced activation of prostaglandin E2 and cyclic AMP production in rat hypothalamus: A mechanism involving inhibition of nitric oxide synthase”, Ilham Bettahi1, Juan M. Guerrero1, Russel J. Reiter2, Carmen Osuna1,* Journal of Pineal Research, Volume 25, Issue 1, pages 34–40, August 1998
http://onlinelibrary.wiley.com/doi/10.1111/j.1600-079X.1998.tb00383.x/abstract
“Role of the Prostaglandins in Norepinephrine Release during Augmented
Renal Sympathetic Nerve Activity in the Dog” JUAN A. OLIVER, ROBERT R. SCIACCA, JOHN PINTO, AND PAUL J. CANNON, Circ Res 48: 835-843, 1981
http://circres.ahajournals.org/content/48/6/835.full.pdf
“Modulation of Norepinephrine Release from Sympathetic Neurons of the Rabbit Aorta by Prejunctional Prostanoid Receptors”, TENNA JUUL JENSEN and OVE A. NEDERGAARD, JPET 291:7–11, 1999
http://jpet.aspetjournals.org/content/291/1/7.full.pdf
“Norepinephrine enhances the LPS-induced expression of COX-2 and secretion of PGE2 in primary rat microglia “, Johannes CM Schlachetzki1,2†, Bernd L Fiebich1*†, Elisabeth Haake1, Antonio CP de Oliveira1, Eduardo Candelario-Jalil3, Michael T Heneka4, Michael Hüll1*, BioMed Central Ltd. 2010
www.biomedcentral.com/content/pdf/1742-2094-7-2.pdf
Effects of norepinephrine and other pharmacological agents on prostaglandin E2 release by rabbit and bovine irides.” Sardar Y.K. Yousufzai, Ata A. Abdel-Latif,
Experimental Eye Research, Volume 37, Issue 3, September 1983, Pages 279–292
http://www.sciencedirect.com/science/article/pii/001448358390163X
“Changes in the Hypothalamic Interaction between Norepinephrine and Prostaglandin E2 during Sexual Maturation in Female Rats” Franchi A. · Gimeno M. · Szwarcfarb B. · Carbone S. · Rondina D. · Moguilevsky J.A
http://www.karger.com/Article/Abstract/127008
“Diminished Prostaglandin-Mediated Inhibition of Norepinephrine Release from the Sympathetic Nerve Endings in Spontaneously Hypertensive Rats”, Kazushi Tsuda1, Ichiro Nishio1 and Yoshiaki Masuyama1 , Clinical and Experimental Hypertension, 1987, Vol. a9, No. 10 , Pages 1601-1614
http://informahealthcare.com/doi/abs/10.3109/10641968709159005?journalCode=ceh
“The Effect of Prostaglandin E2 and Indomethacin on the Placental Vascular Response to Norepinephrine” Anne Berssenbrugg, Debra Anderson, Terrance Phernetton, John H. G. Rankin, Exp Biol Med (Maywood) November 1978 vol. 159 no. 2 281-285http://ebm.sagepub.com/content/159/2/281.abstract
Prostagladnin E2 (PGE2) and cancer examples:

1. “Cancer-stimulated mesenchymal stem cells create a carcinoma stem cell niche via prostaglandin E2 signaling.” – http://www.ncbi.nlm.nih.gov/pubmed/22763855 ;
2. “Interleukin-17 and prostaglandin E2 are involved in formation of an M2 macrophage-dominant microenvironment in lung cancer.” –http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378786/pdf/nihms369069.pdf ;
3. “The role of the EP receptors for prostaglandin E2 in skin and skin cancer.” –http://www.ncbi.nlm.nih.gov/pubmed/22012553 ;
4. “Prostaglandin E2 EP receptors as therapeutic targets in breast cancer.” –http://www.ncbi.nlm.nih.gov/pubmed/22002714
Here is a simple, natural anti-PGE2 drug “Resolvin” : Omega-3 + Aspirin or water willow’s salicin –http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186038/pdf/medrep-03-19.pdf;http://en.wikipedia.org/wiki/Resolvin

How Does Aquila Anal-Breathing (Altair) QiGong Exercises boost your brain and endocrine function?

Aquila Qigong practices increase sex hormones  via the stimulation (stretching/compression, twisting, or/and contraction, even light or thermal )  of  the local peripheral hormonal target tissues ( extragonadal ) which have sex hormone receptors (as intracrinology, http://www.ncbi.nlm.nih.gov/pubmed/1838082, andhttp://www.ncbi.nlm.nih.gov/pubmed/1314080) , as well as the stimulation of the central  hypothalamicpituitarygonadal axis (also HPG axis) known as the neuro-endocrine function  – http://www.uthsc.edu/endocrinology/documents/ch08-syllabus-Childress.pdf.

17 beta-hydroxysteroid dehydrogenase is a group of the liver Cytochrome P450 alcohol oxidoreductases, responsible for catalysing the dehydrogenation of 17-hydroxysteroids in steroidogenesis  that includes interconversion of DHEA and androstenediolandrostenedione and testosterone, and estrone and estradiol, respectively,  as shown in http://upload.wikimedia.org/wikipedia/commons/1/13/Steroidogenesis.svg.

The intracrinologic function takes effect in about  5-10 minutes after starting exercising, while the neuro-endocrine function kicks in after taking a rest.

My theory about the exercise effects on the nervous function, skin/muscle endocrine function (aslo known as intracrinology – steroidogenesis in peripheral intracrine tissues – http://www.ncbi.nlm.nih.gov/pubmed/1838082,  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710002/pdf/11-14.pdf , http://physrev.physiology.org/content/physrev/88/4/1379.full.pdf  and http://www.medizin.uni-tuebingen.de/transfusionsmedizin/institut/eir/content/2004/42/article.pdf  ) , and neuroendocrine function is:

1. Somatic motoring nerves activates the cells in the muscles for the skin and muscle endocrine function (steroidogenesis) with the liver P450 enzymes, leading to syntheses of hGH, DHEA, testosterone, DHT and neurotransmitters and their precursors (Sunlight UV stimulates the skin endocrine function too), for examples: http://www.ncbi.nlm.nih.gov/pubmed/8092980http://www.ncbi.nlm.nih.gov/pubmed/23435015 ,http://www.ncbi.nlm.nih.gov/pubmed/22166417, http://www.ncbi.nlm.nih.gov/pubmed/24464446 & http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847208/pdf/1471-2369-14-194.pdf , http://jap.physiology.org/content/96/2/531.full.pdf+html, http://www.ncbi.nlm.nih.gov/pubmed/15942766;

2. Stretching or twisting of nerves, blood vessels and muscles generates the somatic sensory nervous signals, partially to autonomic nervous reflex arcs in the spine and the medulla oblongata for steroidogenesis of internal smooth muscles, activation of the neuroendocrine function, and partially to the thalamus (via the somatic sensory pathway of the Thalamus) for activation of the central nervous system ,
for examples:
http://www.ncbi.nlm.nih.gov/books/NBK10950/ ;http://www.ncbi.nlm.nih.gov/pubmed/11240404 and more in References). Note: some researcher have shown that “a role of skeletal muscle as a secretory organ of cytokines and other peptides, denominated myokines (IL6, IL8, IL15, Brain-derived neurotrophic factor, and leukaemia inhibitory factor), which have autocrine, paracrine, or endocrine actions and are deeply involved in inflammatory processes” ( http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710002/ and http://physrev.physiology.org/content/physrev/88/4/1379.full.pdf ).

You can boost your growth hormone level over 300 % before a meal in 30 minutes. The best time to jump your hormonal level up is before breakfast.  However, you should limit your exercise duration for no longer than 60-80 minutes – http://jap.physiology.org/content/96/2/531.full.pdf+html . According this report, you can increase your testosterone level at about 20-30%. Our reader also reported this result.

Effects of Exercises on your body: CARBOHYDRATES, HORMONES, AND ENDURANCE PERFORMANCE
This study was done by Davis & Brown, Sport Science Exchange, 80, Vol. 14, NO. 1

exercises-induced endocrine functionHowever, prolonged, heavy-duty, hard-core exercises usually burn out your testosterone faster than your body produces ( http://jap.physiology.org/content/96/2/531.full.pdf+html ). In addition, the hypothalamus and adrenal glands turn dopamine to norepinephrine, and then, when the dopaminergic system runs down in the exhaustion state, the pituitary gland releases excessive prolactin; as a result of combination of both norepinephrine and prolactin, norepinephrine is bound into the sympathetic nervous alpha receptors to tighten up your muscles and arteries, and the cells in the joints and muscles release excessive prostaglandin E2 for pain to set the alarm off – ( http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3766664/ ; http://www.ncbi.nlm.nih.gov/pubmed/22151605 ; http://www.ncbi.nlm.nih.gov/pubmed/10090630 ; http://www.ncbi.nlm.nih.gov/pubmed/15942766).

At this stage, there s a lack of blood flow to your brain and testicles; thus, your testicular function slows down and produces less testosterone. Therefore, you will have a longer and longer recovery time. You may grow your muscles at the expense of your testicular (or ovarian for female ) function –
http://www.ncbi.nlm.nih.gov/pubmed/19092301 ,
http://www.ncbi.nlm.nih.gov/pubmed/11254889,
and http://www.ncbi.nlm.nih.gov/pubmed/14964440 ).

To avoid this problem, instead of hardcore exercises, you can have my Aquila Anal-breathing Qigong exercises once or twice a day
https://www.youtube.com/watch?v=stGUWgNwips
https://www.youtube.com/watch?v=Wlow3ukCud4
https://www.youtube.com/watch?v=pRiChK0Q_FI

Note: Exercises can become addictive, for good –
http://www.ncbi.nlm.nih.gov/pubmed/24001300
http://www.ncbi.nlm.nih.gov/pubmed/22073029
http://www.ncbi.nlm.nih.gov/pubmed/22216780

References:
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4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120765/
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9. http://rspb.royalsocietypublishing.org/cgi/pmidlookup?view=long&pmid=23173208
10. The Somatic Sensory Components of the Thalamus – Neuroscience – NCBI Bookshelf –  http://www.ncbi.nlm.nih.gov/books/NBK10950/
Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001.

11.mEur J Appl Physiol Occup Physiol. 1996;73(5):427-33. Does functional alteration of the gonadotropic axis occur in endurance trained athletes during and after exercise? A preliminary study. Duclos MCorcuff JBRashedi MFougere VManier http://www.ncbi.nlm.nih.gov/pubmed/8803502

12. J Endocrinol Invest. 2008 Oct;31(10):932-8.  Effects of endurance exercise on the reproductive system of men: the “exercise-hypogonadal male condition”.  Hackney AC. http://www.ncbi.nlm.nih.gov/pubmed/19092301

13. Curr Pharm Des. 2001 Mar;7(4):261-73. Endurance exercise training and reproductive endocrine dysfunction in men: alterations in the hypothalamic-pituitary-testicular axis. Hackney AChttp://www.ncbi.nlm.nih.gov/pubmed/11254889

14. Sports Med. 1995 Oct;20(4):251-76. Blood hormones as markers of training stress and overtraining. Urhausen AGabriel HKindermann W. http://www.ncbi.nlm.nih.gov/pubmed/8584849

15. J Nov Physiother. 2013 Feb 16;3(125). pii: 11717. Overtraining, Exercise, and Adrenal Insufficiency. Brooks KCarter J. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648788/pdf/nihms-462899.pdf

16.  Acta Physiol Hung. 2005;92(2):121-37. Testosterone and endurance exercise: development of the “exercise-hypogonadal male condition”. Hackney ACMoore AWBrownlee KK. http://www.ncbi.nlm.nih.gov/pubmed/16268050

17.  J Endocrinol Invest. 2014 Jan;37(1):13-24. doi: 10.1007/s40618-013-0006-0. Epub 2014 Jan 8. Testosterone responses to standardized short-term sub-maximal and maximal endurance exercises: issues on the dynamic adaptive role of the hypothalamic-pituitary-testicular axis. Sgrò PRomanelli FFelici FSansone MBianchini SBuzzachera CFBaldari CGuidetti LPigozzi FLenzi ADi Luigi L. http://www.ncbi.nlm.nih.gov/pubmed/24464446

18.  Am J Physiol Endocrinol Metab. 2012 Apr 15;302(8):E972-8. doi: 10.1152/ajpendo.00573.2011. Epub 2012 Feb 7. The phosphodiesterases type 5 inhibitor tadalafil reduces the activation of the hypothalamus-pituitary-adrenal axis in men during cycle ergometric exercise. Di Luigi LSgrò PBaldari CGallotta MCEmerenziani GPCrescioli CBianchini SRomanelli FLenzi AGuidetti L. http://ajpendo.physiology.org/content/ajpendo/302/8/E972.full.pdf

19. J Clin Endocrinol Metab. 2008 Sep;93(9):3510-4. doi: 10.1210/jc.2008-0847. Epub 2008 Jun 17. The type 5 phosphodiesterase inhibitor tadalafil influences salivary cortisol, testosterone, and dehydroepiandrosterone sulphate responses to maximal exercise in healthy men. Di Luigi LBaldari CSgrò PEmerenziani GPGallotta MCBianchini SRomanelli FPigozzi FLenzi AGuidetti L. http://press.endocrine.org/doi/pdf/10.1210/jc.2008-0847

20. Int J Sports Med. 2008 Feb;29(2):110-5. Epub 2007 Jul 5. The long-acting phosphodiesterase inhibitor tadalafil does not influence athletes’ VO2max, aerobic, and anaerobic thresholds in normoxia. Di Luigi LBaldari CPigozzi FEmerenziani GPGallotta MCIellamo FCiminelli ESgrò PRomanelli FLenzi AGuidetti L. http://www.ncbi.nlm.nih.gov/pubmed/17614028

21. Med Sci Sports Exerc. 2001 Dec;33(12):2029-35. Acetylsalicylic acid inhibits the pituitary response to exercise-related stress in humans. Di Luigi LGuidetti LRomanelli FBaldari CConte D. http://www.ncbi.nlm.nih.gov/pubmed/11740295

22. Eur J Appl Physiol. 2003 Apr;89(2):177-83. Epub 2003 Feb 1. The influence of aspirin on exercise-induced changes in adrenocorticotrophic hormone (ACTH), cortisol and aldosterone (ALD) concentrations. Przybyłowski JObodyński KLewicki CKuźniar JZaborniak SDrozd SCzarny WGarmulewicz M. http://www.ncbi.nlm.nih.gov/pubmed/12665982

23.  2009 PH.D Thesis:  New evidence for the short-term effects of testosterone and cortisol upon athletic performance and training adaptation in elite male rugby players
Blair T. Crewther,  Southern Cross University http://epubs.scu.edu.au/cgi/viewcontent.cgi?article=1161&context=theses

24. STUDIES IN SPORT, PHYSICAL EDUCATION AND HEALTH 196,  Acute Neuromuscular, Cardiorespiratory and Endocrine Responses and Chronic Adaptations
to Combined Strength and Endurance Training in Recreationally Endurance Trained Men and Women, Ritva Sofia Taipale, the Faculty of Sport and Health Sciences of the University of Jyväskylä,in Auditorium S212, on August 31, 2013 https://jyx.jyu.fi/dspace/bitstream/handle/123456789/42016/978-951-39-5343-0.pdf?sequence=2

25. Eur J Appl Physiol. 2005 Aug;94(5-6):505-13. Epub 2005 Jun 8. Influence of exercise duration on post-exercise steroid hormone responses in trained males.Tremblay MS, Copeland JL, Van Helder W http://www.ncbi.nlm.nih.gov/pubmed/15942766

26. J Appl Physiol (1985). 2004 Feb;96(2):531-9. Epub 2003 Sep 26. Effect of training status and exercise mode on endogenous steroid hormones in men. Tremblay MS, Copeland JL, Van Helder W. http://jap.physiology.org/content/96/2/531.full.pdf+html

27.nClin Endocrinol (Oxf). 2012 February; 76(2): 272–280. Non-steroidal anti-inflammatory drug use and levels of estrogens and androgens in men, Margaret A. Gates,1 Andre B. Araujo,1 Susan A. Hall,1 Gary A. Wittert,2 and John B. McKinlay1 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219794/pdf/nihms313719.pdf

28. Behav Brain Res. 2013 Jun 15;247:34-9. doi: 10.1016/j.bbr.2013.03.007. Epub 2013 Mar 13.  Forced and voluntary exercises equally improve spatial learning and memory and hippocampal BDNF levels. Alomari MAKhabour OFAlzoubi KHAlzubi MA. http://www.ncbi.nlm.nih.gov/pubmed/23499703

29. J Appl Physiol (1985). 2012 Oct 15;113(8):1260-6. doi: 10.1152/japplphysiol.00869.2012. Epub 2012 Aug 30. Voluntary resistance running with short distance enhances spatial memory related to hippocampal BDNFsignaling. Lee MCOkamoto MLiu YFInoue KMatsui TNogami HSoya H. http://jap.physiology.org/content/113/8/1260.full.pdf+html

30. Baillieres Clin Endocrinol Metab. 1994 Apr;8(2):451-74. Structure, regulation and role of 3 beta-hydroxysteroid dehydrogenase, 17 beta-hydroxysteroid dehydrogenase and aromatase enzymes in the formation of sex steroids in classical and peripheral intracrine tissues. Labrie FSimard JLuu-The VPelletier GBelghmi KBélanger A. http://www.ncbi.nlm.nih.gov/pubmed/8092980

31.  Mol Cell Endocrinol. 1991 Jul;78(3):C113-8. Intracrinology. Labrie F. http://www.ncbi.nlm.nih.gov/pubmed/1838082

32. J Mol Endocrinol. 2000 Aug;25(1):1-16. Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease. Labrie FLuu-The VLin SXSimard JLabrie CEl-Alfy MPelletier GBélanger A. http://jme.endocrinology-journals.org/content/25/1/1.long

33. J Steroid Biochem Mol Biol. 1992 Mar;41(3-8):597-603. Distribution of 17 beta-hydroxysteroid dehydrogenase gene expression and activity in rat and human tissues. Martel CRhéaume ETakahashi MTrudel CCouët JLuu-The VSimard JLabrie Fhttp://www.ncbi.nlm.nih.gov/pubmed/1314080

34. J Clin Endocrinol Metab. 2000 Dec;85(12):4841-50. Tissue- and site-specific gene expression of type 2 17beta-hydroxysteroid dehydrogenase: in situ hybridization and specificenzymatic activity studies in human placental endothelial cells of the arterial system. Bonenfant MBlomquist CHProvost PRDrolet RD’Ascoli PTremblay Yhttp://press.endocrine.org/doi/pdf/10.1210/jcem.85.12.7040

35. Endocrine. 2011 Oct;40(2):203-11. doi: 10.1007/s12020-011-9519-5. Epub 2011 Aug 30. Human type 2 17beta-hydroxysteroid dehydrogenase in umbilical vein and artery endothelial cells: differential inactivation of sex steroids according to the vessel type.Simard MDrolet RBlomquist CHTremblay Y. http://www.ncbi.nlm.nih.gov/pubmed/21877158

36. Biochem. J. (1996) 314, 839±845 (Printed in Great Britain) 839
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37. J Steroid Biochem Mol Biol. 2013 Sep;137:107-23. doi: 10.1016/j.jsbmb.2013.02.006. Epub 2013 Feb 19. Steroidogenesis in the skin: implications for local immune functions.Slominski AZbytek BNikolakis GManna PRSkobowiat CZmijewski MLi WJanjetovic ZPostlethwaite AZouboulis CCTuckey RChttp://www.ncbi.nlm.nih.gov/pubmed/23435015

Orgasm , Histamine Receptors ( H1, H2 and H3) , and Premature Eejaculation

Orgasm releases extra histamine by mast cells under the stimulation of norepinephrine due to an rapid conversion of dopamine-to-norepinephrine in the hypothalamus and adrenal glands during sexual encounter and even after orgasm.
The solution is: reduce abrupt dopamine-norepinephrine conversion, and inhabit its action on the adrenergic alpha receptors.

The receptors affected by histamine are given below.  H2 seems producing positive effects, but H1 can give you positive and some negative (such as itching, asthma, pain, dizziness, an so on) effect,  and H3, which serves as a feeback control of norepinephrine release but also negatively inhibit acetylcholine and serotonin release in the CNS for memory loss, depression and weak cholinergic/vegas and serotonin nervous control.  Thus, H1 and H3 receptors generate sexual exhaustion symptoms, although H1 receptors in the vaginal endothelial cells (particularly, around the G-spot) triggers the orgasm responses for the vagal nerves, and in the prostate, urethra, bulbourethral,  and seminal vesicles, it produces hypersensetive sensation and induces ehaculation urgency premature ejaculation or precum/semen leakage during sexual encounter .

Premature ejaculation is a very complicated tissue.
Main possible causes:
1. The prostate abrasion and poor seminal quality due to over-masturbation.
It requires a long-term prostaglandin E-1 therapy with Viapal-hGH-J (3-015) and 5-HTP (2-001) ,  plus Fish oil  (2-005) and Vitamin D(2-004) daily.
http://www.actionlove.com/mail/herbform.htm
2.  Drug abuse.
It requires a long-term nervous detoxification with Viapal-hGH-J (3-015) , DeToxiA (1-017) and 5-HTP (2-001), plus Fish oil  (2-005) and Vitamin D(2-004) daily.
http://www.actionlove.com/cases/case11500.htm

3.  a low  Serotonin level in the brain.
MoodMax and 5-HTP can help
4.  over-training of the nervous L1-L3 reflex arcs  of the PC and prostate muscles.
a long term Anal breathing practice can solve the problem
http://www.actionlove.com/cases/case11237.htm
 http://www.actionlove.com/cases/case10501.htm
http://www.actionlove.com/cases/case9323.htm
http://www.actionlove.com/cases/case9266.htm
http://www.actionlove.com/cases/case9212.htm
http://www.actionlove.com/cases/case9194.htm

5.  weak erection.
Power your erection with Viapal-hGH-J (3-015)

We use 5-HP,  ViaGrowth-III (or ViaGrowth-IV)+ MoodMax + DopaFIbra, Fish Oil (Omega-3 EPA  (647 mg) and Vitamins D 2000 IU and E 200 IU.
5-HTP + MoodMax + EPA  boost the cholinergic,  serotonin and GABA nervous control in the hypothalamic dopamine-norepeinephrine conversion, and power the parasympathetic nervous function to counterbalance  the sympathetic nervous function.
Our 5-HTP also contains a high dose of B3 (Niacin) to increase prostaglandin D2 production for relax the blood-brain tight junction for brain and nervous nutrients to penetrate into the brain and nervous system. Prostaglandin D2 also dilates arteries and capillaries for better blood circulation. B3 also increases the serotonin synthesis.
DopaFibra + ViaGrowth-III increase androgen hormones,  charge the central  dopaminergic nervous system and the parasympathetic nervous system,  and block the adrenergic alpha receptors, so that norpeinephrine and epinephrine can stimulate the adrenergic beta receptors for arterial dilation,  more blood flow and beta-endorphin release.   Beta-endorphin in the brain and semen can cool down the sympathetic nervous function.
Fish Oil, Vitamins D and E will also increase testosterone and semen production.  They also change the semen chemistry by increasing prostaglandin E1 and E3 while reducing prostaglandin E2.
Reducing the sympathetic nervous function, increasing beta-endorphin/acetylcholine/serotonin/GABA/prostaglaninds E1/E2 and nadrogen hormone testosterone/DHT, and reducing norepinephrine/prostaglandin E2 will reduce histamine release.
Premature ejaculation, the sympathetic nervous fight response to sexual stimulation,  occurs when the prostate,  seminal vesicles, urethra, and  bulbourethral glands cook up more prostaglandin E2 and histamine, as inflammatory and sensitization hormones, in the synthesizing fluids (precum and semen)  under the sexual-induced excessive hypothalamic and adrenal dopamine- norepinephrine conversion.
We use the same formula to knock the bladder anxiety, over-reactive bladder, and stress induced incontinence.
There is another sympathetic nervous response to sex,  known as sympathetic nervous flight.  When the dopamine nervous function becomes too weak to stimulate the pituitary glands for sex, the pituitary gland releases insufficient oxytocin but excessive prolactin to constrict the arteries and retrieve the blood from the brain, penis and testicles, so that the penis goes limp.  The sympathetic nervous flight response to sex will force you to contract the PC muscles and the prostate to stimulate L1-L3 and S2-S4 for erection. Stimulation of L1-L3 sympathetic nerves activates the autonomic/sympathetic nervous reflex arcs in Discs L1 – L3 for precum release, semen emission and expulsion (ejaculation).
The solution for the sympathetic-nervous-flight-induced the sympathetic nervous fight is to block the autonomic nervous reflex arcs in Discs L1-L3 by my Anal Breathing training that alternates the autonomic nervous reflex arcs from L1-L3 to S1-S4.
Chronic masturbation for a fast ejaculation release usually trains the L1-L3 autonomic reflex arcs into a neuroplasticity state. If you got it, you have to ee-train your nervous reflex arcs.
Here are the references for Anal Breathing;
https://www.facebook.com/photo.php?fbid=10151708146338125&set=a.119650343124.125193.558153124&type=1&theater
http://www.youtube.com/watch?v=CMxQDc3VQA8
http://www.youtube.com/watch?v=stGUWgNwips

Histamine receptors (From wikipedia – http://en.wikipedia.org/wiki/Histamine
Receptor                 Mechanism      Function  Antagonists    (Drugs)
H1   Gq
H2   Gs
↑ Ca2+
H3   Gi
H4   Gi
Type
Location                                       Function
H1 histamine receptor Found on smooth muscleendothelium, and central nervous system tissue Causes bronchoconstriction, bronchial smooth muscle contraction, vasodilation, separation of endothelial cells (responsible for hives), and pain and itchingdue to insect stings; the primary receptors involved in allergic rhinitis symptoms and motion sickness; sleep and appetite suppression.
H2 histamine receptor Located on parietal cells and vascular smooth muscle cells Primarily involved in vasodilation. Also stimulate gastric acid secretion
H3 histamine receptor Found on central nervous system and to a lesser extent peripheral nervous system tissue Decreased neurotransmitter release: histamine, acetylcholinenorepinephrineserotonin
H4 histamine receptor Found primarily in the basophils and in the bone marrow. It is also found on thymussmall intestinespleen, and colon. Plays a role in chemotaxis