May 13, 2010

Females may harbor biological “inner male”

n adult fe­male mice, switch­ing off one gene seems to start turn­ing the ovaries in­to tes­ti­cles and trig­gers the pro­duct­ion of male hor­mones at nor­mal male levels, sci­en­tists say.

The cu­ri­ous find­ings have led two re­search­ers to re­mark in a pub­lished pa­per that, bi­o­log­ic­ally speak­ing, fe­males may be en­gaged in a life­long “bat­tle to sup­press their in­ner ma­le.”

Both pa­pers ap­pear in the Dec. 11 is­sue of the re­search jour­nal Cell.

In a­dult fe­­male mice, switch­ing off one gene starts turn­ing the ovaries in­­to tes­ti­cles that pro­duce male hor­mones, sci­en­tists say. Above, John Couse, bi­ol­o­gist in the Na­tion­al In­sti­tute of En­vi­ron­men­tal Health Sci­ences and author of a pre­vious study on ro­dent "sex re­ver­sal," holds a fe­male mouse. (Im­age cour­te­sy U.S. Nat'l Inst. of En­vi­ron­men­tal Health Sci­ences)

The new results echo a pre­vious study that found that fe­male ovar­ian tissues in mice start to con­vert to male-like tis­sues in the ab­sence of sig­nals from es­tro­gen, a fe­male sex hor­mone. That stu­dy ap­peared in the Dec. 17, 1999 is­sue of the jour­nal Science.

In the newer re­search, N. Hen­ri­ette Uh­len­haut of the Eu­ro­pe­an Mo­lec­u­lar Bi­ol­o­gy Lab­o­r­a­to­ry in Hei­del­berg, Ger­ma­ny, and col­leagues were stu­dy­ing genes that dur­ing de­vel­op­ment are re­spon­si­ble for con­vert­ing glands called go­nads in­to ei­ther ovaries or tes­ti­cles, de­pend­ing on the sex.

Ovaries produce eggs, the fe­male sex cells, while tes­ti­cles produce sperm.

Uh­len­haut and col­leagues ge­net­ic­ally en­gi­neered mice in which the ac­ti­vity of a called Fox2L could be chem­ic­ally sup­pressed in the ovaries.

Fox2L, in turn, is a reg­u­la­tor gene that in­flu­ences the lev­el of ac­ti­vity of an ar­ray of oth­er genes. Among oth­er things, it keeps in check genes that tend to pro­mote tes­ti­cle de­vel­op­ment, ac­cord­ing to Uh­len­haut’s group.

Switch­ing off Fox2L had the im­me­di­ate ef­fect of in­creas­ing the lev­el of ac­ti­vity of some of these “tes­tis-specific” genes, the sci­en­tists re­ported. Crit­i­cal among these, they iden­ti­fied one called Sox9.

Con­com­i­tant with the boost in Sox9 ac­ti­vity was a “re­pro­gram­ming” of cer­tain ovar­i­an cell lin­eages in­to what ap­peared to be tes­tis cell lin­eages, Uh­len­haut and col­leagues found. Mean­while, the mod­i­fied ovaries be­gan pro­duc­ing nor­mal ma­le-like lev­els of the hor­mone tes­tos­ter­one.

“Our re­sults show that main­te­nance of the ovar­i­an phe­no­type [form] is an ac­tive pro­cess through­out life,” the sci­en­tists wrote.

It’s un­clear wheth­er the find­ings would trans­late to hu­mans, but be­cause mice share over 90 per­cent of their genes with hu­mans, it very of­ten hap­pens that mouse pro­cesses have par­al­lels in hu­mans.

It would seem “tes­tic­u­lar de­vel­op­ment is ac­tively re­pressed through­out the life of fe­ma­les,” added An­drew Sin­clair and Craig Smith of the Mur­doch Chil­dren’s Re­search In­sti­tute in Mel­bourne, Aus­tral­ia, in a pa­per pub­lished in the same is­sue of Cell. Sin­clair and Smith—the re­search­ers who in their ar­ti­cle metaphoric­ally sug­gested an “in­ner ma­le” may lurk with­in all fe­ma­les—also not­ed the find­ings go against “con­ven­tional wis­dom” that the ova­ry and tes­tis are “ter­mi­nally dif­fer­en­ti­ated,” or ir­re­versibly de­vel­oped to their ma­ture state.

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