Sexual Differentiation is the story of how hormones interact with the body's genes to affect the development of the body and the brain to result in sex-specific behaviors and traits in the adult.

We are all probably most familiar with species that have 2 sexes. This is called gonochorism (meaning specialized gonads/gamete production) or dioecious (mean 2 sexes specialized in gamete production). There are also species that are monoecious (hermaphodites) where individuals engage in sexual reproduction, but all members of a species produce both types of sexual organs (and gametes). There are also partenogenetic species (literally virgin birth) where reproduction is asexual - no gametes are passed between members of the species.

In placental mammals:

Sex is determined by the sex chromosomes. (female XX & male XY).

Born with:

1) Bipotential gonads (can become either testes or ovaries)

2) Muellerian duct system (female internal organs: fallopian tubes, uterus internal vagina) and Wolffian duct system (masculine internal organs (vas deferns, seminal vesicles, prostate, epididymus)

3) Bipotential external genitalia

GENETIC SEX DETERMINES GONADAL SEX

The gene called TDF (testes determination factor) is on the 'Y' chomosome, and it is the presence of this gene that causes the bipotential gonads to become testes. In the absence of the expression of the TDF gene, the gonads become ovaries.

2. GONADAL SEX DETERMINES PHENOTYPIC SEX (phenotype = physical characteristics of an individual).

Testicular secretions drive the masculinization of the reproductive system.

a. MRF (Muellerian Regression Factor) a protein hormone induces regression of the Muellerian duct system.

b. testosterone a steroid - makes specific types of cells in the Wolffian system develop the masculine internal sex organs; testosterone is converted to dihydrotestosterone (DHT) by the enzyme 5alpha-reductase found in the cells of the peripheral genitalia, masculinizes the external genitalia.

** In the absence of any hormones the phenotypic sex becomes feminine, so if hormones are not present, it is as important as is they are.

--> For successful sexual differentiation of the male, need the receptors for testosterone and MRF.

GENETIC DEFECTS of sexual differentiation

1. XY - both testes fail to develop (no TDF)

->internal and external sex organs are feminine

2. XY - only one testis develops

-> testosterone is produced by the one testis, and enough is produced to masculinize the external genitalia and Wolffian ducts.

-> MRF acts locally (too diluted by the time it reaches other side of the body) so it only masculinizes one side, where it causes the Muellerian ducts on the same side as the testis to regress. The Muellerian ducts on the other side survive.

"hermaphrodite" both sexual organs present.

phenotype=masculine (occasionally ambiguous)

3. XX ovaries fail to develop

feminine internal and external genitalia (except for the absence of ovaries)

4. XY androgen receptors absent (Androgen Insensitivity Syndrome also called Testicular Feminization Mutation)

do not make androgen receptors, so do not respond to androgen

- mutation on the X chromosome (recessive)

Testes develop normally and secrete MRF as well as testosterone. Muellerian ducts regress, but genitalia develop as a female. The Wolffian system regresses due to the lack of estrogen receptors.

May not develop until puberty, when the lack of menstruation may bring it to a doctor's attention

Breast development occurs because testes also secrete estrogen. It is the estrogen/testosterone ration (during developmental years) that determines breast development. In the absence of testosterone receptors, even a small amount of estrogen is interpreted as a high E/T ratio.

5. XY 5alpha-reductase absent

Born with ambiguous genitalia because DHT is needed to masculinize external genitalia. The rise in testosterone at puberty results in masculinization at puberty. Known as 'guevedoces' in the Dominican Republic where there is an area where there is a high concentration of this genetic defect. Guevedoce means literally 'penis at twelve', as the condition is recognized as existing in this culture. Will see more of this in the film The Fight To Be Male, next week.

SOME ARTICLES THAT YOU MIGHT FIND INTERESTING:

Allen, L. S. and Gorski, RA Sexual orientation and the size of the anterior commisure in the human brain. Proceedings of the National Academy of Science, USA, 89:7199-7202 (1992).

Gaulin, SJC, Fitzgerald, RW, and Wartell, MS Sex differences in spatial ability and activity in two vole species. J. Comp Psychology, 104:88-93 (1990)..