The most common congenital disorders of all, especially in baby boys, are differences in a newborns sexual anatomy that is not standard female or male. In boys, they include undescended testicles, misplaced urethras, and improperly developed internal organs.
Some of these disorders may be treated with surgery and some also with hormonal supplementation. Scientists are troubled because the incidence of these disorders is increasing, especially in developed countries. While causes are unknown, researchers suspect that endocrine disruptors from environmental contaminants may be involved.
Joan Jorgensen
Its hard to know how something goes wrong if you dont know how it goes right, says Joan Jorgensen, a professor of comparative biosciences in the University of WisconsinMadison School of Veterinary Medicine.
So, Jorgensen, lead author Anbarasi Kothandapani, and others have set out to understand how functional reproductive systems are formed. Over several years, they studied how one gene, GLI3, coordinates the precisely timed development of the male reproductive organs. Using a mouse model, they discovered that GLI3 promotes the growth of the only cells capable of producing male hormones in a fetus. Without enough of those cells, development goes awry.
The researchers published their findings June 4 in the journal PLOS Genetics. Their works helps us understand how genes and hormones interact to develop male reproductive systems, a step toward researching why disorders in these organs have become more common and how we might prevent them.
The Jorgensen lab has long studied male and female sex differentiation in developing mice. Altogether, a male fetus must successfully have testes descend toward the scrotum, differentiate external genitals, and develop internal organs such as the prostate. Much of this process is controlled by a genetic pathway whimsically named Hedgehog after the gene was discovered in flies covered in bristles and hormones. The two most important hormones are testosterone and another named INSL3.
The GLI3 gene is part of the Hedgehog gene pathway and mutations in the gene are linked to reproductive tract disorders in humans. To study how GLI3 works, the Jorgensen lab turned to a line of mice carrying a mutation that models human mutations in the gene. In mice, the mutation is lethal before birth, so they had to study its effects in developing embryos.
The first thing we wanted to do was see if they had the same reproductive organ phenotypes as human patients, says Jorgensen. These problems include undescended testicles and disorders in urethra placement.
The mutant mice had several defects similar to humans with mutations in the gene. They experienced delays in the descent of their testicles within their abdomens And in about half of the mutants, the urethra opened at the base of the penis instead of at the tip.
Suspecting a problem with the hormone-producing cells called Leydig cells, the researchers examined the testes. Although mutant mice had typical-looking gonads, Jorgensens team saw their testes had fewer Leydig cells and these cells even grew weaker as the embryos developed.
We concluded that the cells started off okay, but they werent able to maintain their identity and they lost their function, says Jorgensen. Over time, they werent able to increase the amount of androgen synthesis needed to make sure everything develops properly.
The researchers discovered that the Hedgehog pathway, through GLI3, stimulates the formation of Leydig cells, which produce the hormones necessary to develop male sex organs. And those hormones go on to reinforce the Hedgehog pathway, which is vital for developing the prostate and penis. They concluded that most of the defects in the mutant mice could be explained by dysfunctional Leydig cells.
Treating pregnant mice with extra testosterone wasnt enough to correct all the defects, because the GLI3 gene was itself necessary, especially for producing a normal penis. But when the researchers reintroduced the non-mutant GLI3 gene into the mutant testes in culture, they were able to restore production of genes necessary for the production of testosterone.
The upshot is that researchers discovered a complex dance between genes and hormones. Any misstep in the waltz can spell disaster.
There are several environmental disruptors out there that will impact the Hedgehog pathway. When you put that together with genetic mutation, it could make some individuals more susceptible to developmental disorders than others, says Jorgensen.
This improved clarity in how the genes are supposed to function could help researchers understand how environmental toxins might be to blame for a rise in sex development disorders. That understanding is the first step toward prevention.
This work was supported in part by the National Institutes of Health (grants R01HD075079, R01- HD090660, R01-HD090660-S, R01-AR070093, R01-DK110408, and U01-DK110807).
Share via Facebook
Share via Twitter
Share via Linked In
Share via Email
- HGH Infrared Systems Announces Debut of Spynel-S and Product Name Change - April 29th, 2013 [April 29th, 2013]
- Report: Biogenesis documents link A-Rod to HGH - April 29th, 2013 [April 29th, 2013]
- HGH Infrared Systems Announces New Blackbody Products and Updates - April 29th, 2013 [April 29th, 2013]
- "Anti-Aging" Pill SeroVital™-hgh Gets Overwhelming Response in The New York Times Magazine - April 29th, 2013 [April 29th, 2013]
- Radar Online Features Celebrity Makeup Artist's Anti-Aging Secret... SeroVital™-hgh - April 29th, 2013 [April 29th, 2013]
- De Smith says players will not be 'bullied' on HGH testing - April 29th, 2013 [April 29th, 2013]
- Smith says players won't be bullied on HGH test - April 29th, 2013 [April 29th, 2013]
- BraceLand Nutraceuticals - Turn Back Time with HGH - Video - April 29th, 2013 [April 29th, 2013]
- WWE '13 - HGH Clan vs spideysams - Video - April 29th, 2013 [April 29th, 2013]
- 216 Owner - April 29th, 2013 [April 29th, 2013]
- WvW HGH roaming aggressive conditions engineer (100'nades sequel) - Video - April 29th, 2013 [April 29th, 2013]
- WWE"13 WWE"13 xVBIx Pride Owned HGH zBrahmaBullz / My Epic Return - Video - April 29th, 2013 [April 29th, 2013]
- WWE '13 - HGH Clan vs P8909362, MrX206 and Danfort91 - Video - April 29th, 2013 [April 29th, 2013]
- Dr. Ed Park on why TA-65 is better than HGH - iHealthTube 8 - Video - April 29th, 2013 [April 29th, 2013]
- 15 mins HGH (Human Growth Hormone) release with Delta Isochronic - April 29th, 2013 [April 29th, 2013]
- Report: NFL HGH use likely common - May 1st, 2013 [May 1st, 2013]
- Anonymous player: HGH use in NFL 'like clockwork' - May 1st, 2013 [May 1st, 2013]
- HGH in the NFL: A growing menace - May 1st, 2013 [May 1st, 2013]
- HGH use in the NFL, still apparently subject for debate - May 1st, 2013 [May 1st, 2013]
- HGH use 'rampant' in NFL, according to report - May 1st, 2013 [May 1st, 2013]
- Report: HGH Use in NFL Is ‘Rampant,’ ‘Increasing’ With No Blood Test in Place - May 1st, 2013 [May 1st, 2013]
- Report: HGH use increasing - May 1st, 2013 [May 1st, 2013]
- PFT: HGH use reportedly rampant across league - May 3rd, 2013 [May 3rd, 2013]
- WWE '13 - HGH Clan OWNING these T-Rashy ass SPAMMERS - Video - May 3rd, 2013 [May 3rd, 2013]
- League wants HGH testing, needs players to want it, too - May 4th, 2013 [May 4th, 2013]
- WWE '13 - HGH KILLS Vendetta and NK CoLdR - Video - May 6th, 2013 [May 6th, 2013]
- Start Up Suplementos (360°) RENEWAL HGH Workout for Men 30ml Always Young - Video - May 6th, 2013 [May 6th, 2013]
- "Fountain of Youth" Pill SeroVital™-hgh Huge Draw at Annual Gynecology Meeting - May 8th, 2013 [May 8th, 2013]
- hGH Rap (Thrift Shop Parody) - Video - May 8th, 2013 [May 8th, 2013]
- WWE '13 - HGH vs KSA - Video - May 9th, 2013 [May 9th, 2013]
- WWE '13 - HGH Clan vs ObeyCrisz - May 9th, 2013 [May 9th, 2013]
- WWE '13 - HGH Clan vs jaTT253 - May 9th, 2013 [May 9th, 2013]
- WWE '13 - HGH vs The Shield? - Video - May 9th, 2013 [May 9th, 2013]
- WWE '13 - HGH Clan vs The1337Rasengan, Vinodhstanley and Chevyochenta - Video - May 9th, 2013 [May 9th, 2013]
- WWE '13 - HGH Clan OWNS Misfits_Owner, E214Classic and Kieron_Reynolds - Video - May 9th, 2013 [May 9th, 2013]
- WWE '13 - HGH Clan vs bigjoker____, FINAL7ROMANRAT, and VENdeTTA_RIppER - Video - May 11th, 2013 [May 11th, 2013]
- WWE '13 - HGH Clan vs PROOF_WANTED, OcaSs013_NDS and VigilanteWave24 - Video - May 11th, 2013 [May 11th, 2013]
- AhmetKayaGiderim-HGH-vidimob - Video - May 12th, 2013 [May 12th, 2013]
- J-rich94 - May 12th, 2013 [May 12th, 2013]
- WWE '13 - HGH Clan OWNS LordRaiku123 (NK Clan Member) - Video - May 17th, 2013 [May 17th, 2013]
- Footloose - Act One - Scene 4 - A Hgh School Hallway - Video - May 17th, 2013 [May 17th, 2013]
- Genuine HGH Available and AAS - Video - May 18th, 2013 [May 18th, 2013]
- Vlog Diaxu i HGH odc.2 - Video - May 18th, 2013 [May 18th, 2013]
- HGH Hormone Release + 528 Hz Virtual Anti Aging Spa Fatburner Mood Enhancer - Video - May 18th, 2013 [May 18th, 2013]
- WWE '13 - HGH vs 216 - Oh_216_Punk (Owner) and Oh_216_Prophecy - 'Bow Down/I Been On' by Beyonce - Video - May 18th, 2013 [May 18th, 2013]
- HGH Energizer Review By AgeExperts.net - Video - May 20th, 2013 [May 20th, 2013]
- Take me to the king Hgh's flag and banner - Video - May 20th, 2013 [May 20th, 2013]
- Best HGH Supplement - Video - May 21st, 2013 [May 21st, 2013]
- Testosterone - May 22nd, 2013 [May 22nd, 2013]
- Lack of HGH testing leaves hole in drug program - May 23rd, 2013 [May 23rd, 2013]
- Mark Sisson Primal Diet review HGH - May 23rd, 2013 [May 23rd, 2013]
- Humovox HGH Reviews - Supplementing.com - Video - May 23rd, 2013 [May 23rd, 2013]
- Bruce ( Spit ) Kimble - May 24th, 2013 [May 24th, 2013]
- NFL roundup: NFL proposes immediate HGH testing - May 25th, 2013 [May 25th, 2013]
- Report: NFL makes proposal for HGH testing - May 25th, 2013 [May 25th, 2013]
- NFL submitted proposal for immediate HGH testing, according to report - May 25th, 2013 [May 25th, 2013]
- IM A BOSS IN HGH - Video - May 26th, 2013 [May 26th, 2013]
- WWE '13 - HGH vs SMK-Ace_SkillZ (SMK Clan) WEAK BITCHES! - Video - May 28th, 2013 [May 28th, 2013]
- Invigorate HGH Reviews - Supplementing.com - Video - May 28th, 2013 [May 28th, 2013]
- Tarair Returned - 5v5 HGH Elixir Engineer - Video - May 28th, 2013 [May 28th, 2013]
- XxL3GACYxX-_ vs HGH Owner Kavan/BSS Owner Kavan - Video - May 29th, 2013 [May 29th, 2013]
- WWE '13 - HGH vs MOD - Video - May 29th, 2013 [May 29th, 2013]
- Discount Hgh Supplements - Promo Code - Video - May 30th, 2013 [May 30th, 2013]
- WWE '13 - HGH is STILL BETTER THAN NK - Video - May 30th, 2013 [May 30th, 2013]
- HGH Infrared Systems Presents to United 4 Defense, the Growing Cambridge-Based Defense-Technology Networking Group - May 31st, 2013 [May 31st, 2013]
- WWE'13 vs. HGH_LdR_LEVI HGH-Kavan-Owner HGH-Braham_Bullz - Video - May 31st, 2013 [May 31st, 2013]
- Exposing HGH - Video - May 31st, 2013 [May 31st, 2013]
- HGH 800 Hormona del Crecimiento - Video - May 31st, 2013 [May 31st, 2013]
- 2013 NBA Playoffs, Ducks Update, NFL HGH Testing, UFC 160 - May 31st, 2013 [May 31st, 2013]
- Hgh Code - Promo code Code - Video - June 1st, 2013 [June 1st, 2013]
- Hgh Coupon - Coupon Code - Video - June 1st, 2013 [June 1st, 2013]
- Discount Hgh - Coupon code Code - Video - June 3rd, 2013 [June 3rd, 2013]
- Hgh Discount - Discount Code - Video - June 3rd, 2013 [June 3rd, 2013]
- Official HGH Clan™ |Recruiting Videos| - Video - June 3rd, 2013 [June 3rd, 2013]
- Straight Dogged: HGH LDR Gets The Treatment - Video - June 4th, 2013 [June 4th, 2013]
- Increase HGH Naturally - Try RISK FREE - Hype or Real? - Video - June 4th, 2013 [June 4th, 2013]
- Growth Hormone Booster SeroVital®-hgh Causing Frenzy of Excitement at Renowned Sleep Conference - June 6th, 2013 [June 6th, 2013]
- Wwe13 vs HGH CLAN: HGH-Brahma_Bullz - June 6th, 2013 [June 6th, 2013]
- WWE '13 - HGH owns xSinFulxEniGmAx - June 6th, 2013 [June 6th, 2013]
- HGH Energizer Reviews - Video - June 6th, 2013 [June 6th, 2013]