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Intersexo. I - Genes envolvidos na determinaĆ§Ć£o do sexo masculino
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Abstract(s)
RESUMO
Neste artigo actualizamos a embriologia
do sistema reprodutor masculino
e apresentamos a cascata de genes
que controlam a determinaĆ§Ć£o do
sexo (sexo gonĆ”dico) e a diferenciaĆ§Ć£o
sexual (sexo genital). Em artigos subsequentes,
explicaremos o mecanismo
pelo qual as lesƵes destes genes condicionam
intersexo. Na gĆ³nada embrionĆ”ria
bipotente os genes NR5A1(SF1)
e WT1(-KTS) activam o gene SRY, enquanto
que os genes WNT4 e WT1(-
KTS) activam os genes feminizantes
NROB1(DAX1) e SOX3. O SRY dispara
a determinaĆ§Ć£o da gĆ³nada bipotente
em testĆculo ao induzir a diferenciaĆ§Ć£o
em cƩlulas de Sertoli e ao inibir os genes
DAX1 e SOX3. A diferenciaĆ§Ć£o
do sexo Ć© uma consequĆŖncia da interacĆ§Ć£o
entre os genes SOX8, SOX9,
NR5A1, GATA4 e WT1(+KTS), apĆ³s
potenciaĆ§Ć£o pelo SRY. Neste mecanismo,
as cƩlulas de Sertoli segregam
a hormona anti-mulleriana (AMH) e induzem
a diferenciaĆ§Ć£o das cĆ©lulas de
Leydig. A AMH induz a atrofi a do canal
de Muller, inviabilizando o fenotipo feminino.
Sob infl uĆŖncia da gonadotrofi
na coriĆ³nica (HCG), as cĆ©lulas de
Leydig segregam testosterona, a qual
Ć© entĆ£o parcialmente metabolizada em
5-dehidro-testosterona. Sob mediaĆ§Ć£o do gene CFTR, a testosterona promove
a diferenciaĆ§Ć£o do canal de Wolff na
metade reprodutora (canais eferentes,
epidĆdimos, canais deferentes, vesĆculas
seminais, canais ejaculadores),
enquanto que a 5-dehidro-testosterona
induz a diferenciaĆ§Ć£o do canal de Wolff
na metade urinĆ”ria (prĆ³stata, uretra,
pƩnis, escroto). ABSTRACT
In this article we update the embryology
of the male reproductive system
and present the genes that control
sex determination (gonadal sex)
and sex differentiation (genital sex).
In the embryonic bipotent gonad, the
NR5A1(SF1) and WT1(-KTS) genes
interact to activate the SRY gene,
whereas the interaction between the WNT4 and WT1(-KTS) genes activate
the feminizing genes NROB1(DAX1)
and SOX3. SRY then causes the determination
of the bipotent gonad into
the testicle, by inducing Sertoli cell differentiation
and by inhibitting DAX1/
SOX3. Sex differentiation is thereafter
a consequence of SOX8, SOX9,
NR5A1, GATA4 and WT1(+KTS) gene
interaction under SRY potentiation. In
this mechanism, Sertoli cells secrete
the anti-mullerian hormone (AMH) and
cause Leydig cell differentiation. AMH
declanches the atrophy of the Muller
ducts and therein impedes development
of the female phenotype. Under
the control of corionic gonadotrofi n
(HCG), Leydig cells secrete testosterone,
which is then partially metabolized
into 5-dihydro-testosterone. Under the
control of the CFTR gene, testosterone
promotes the differentiation of the Wolff
ducts into a reproductive half (efferent
ducts, epididymis, vasa deferens, seminal
vesicles, ejaculatory ducts), whereas
5-dihydro-testosterone induces the
differentiation of the Wolff ducts into
a urinary half (prostate, uretra, penis,
scrotum).
Description
Keywords
Embriologia testĆculo determinaĆ§Ć£o do sexo diferenciaĆ§Ć£o sexual mecanismos genĆ©ticos Embriology testicle sex determination sexual differentiation genetic mechanisms
Citation
Nascer e Crescer 2005; 14(4): 292-299