Introduction
First of all, in biology the only distinction between male and female is based on the production of gametes. Females product big gametes that are called eggs cell while males product small gametes that are called sperm.
- The first difference is in genes
- The second difference is the exposition to steroids
- The third difference is due to random factors and environmental influence (the intrauterine ambient for example)
Sex is determinated by genes. A male karyotype is XY while a female one is XX.
On the Y chromosome there is an important gene: SRY (Sex determining Region Y). It makes the whole organism develop as males. If it is not expressed the default way is developing as females.
At the beginning the cells of the primordial gonad that lie along the uro-genital ridge are in a bipotential state. SRY is expressed only after the 7th week of gestation. At that very moment the development in the uterus is the same both sexes. There are the same biological structures and tissues. The uro-genital diaphragm is undifferentiated. The pelvic cavity presents two structures: the Wolffian duct and the Mullerian duct.
- If SRY is not present the body develops as females.
Wolffian duct without the trophic effect of testosterone degenerates by apoptosis process while Mullerian duct becomes the Fallopian tube. Ovary develops and starts producing estrogen. Also uterus develops.
- If SRY is present it starts the differentiation to a biological male.
The first effect is the formation of testicles and the production of steroids by them, in particular testosterone. In the main time they produce the MIF (Mullerian Inhibiting Factor) which determinates the atrophy of Mullerian duct. In this phase the peak of testosterone is very important to make the Wolffian duct became vas deferens , also to make prostate develop and uro-genital diaphragm to differentiate into male one.
During male life there are three peak of testosterone:
- 8-12^th week of gestation (it is the critic period)
- At birth
- At puberty
The first peak is very important and testosterone effects are increased by the activity of an enzyme, the 5-alpha-reductase which converts testosterone into dihydrotestosterone.
The exposition to steroids plays an essential role in differentiation. To be more precise its effect is on cells which have receptors: like the Wolffian duct cells and some particular cells of the SNC.
SNC dimorphic structures and physiological differences
Looking at the brain morphology there are some differences between females and males.
- Located into the spinal cord there is the Onuf nucleus where there is a group of motor neurons which innerves muscles like bulbo - cavernosus and ischio - cavernosus. In female they are less developed so this nucleus is smaller than the male one. Testosterone in males makes these muscles become hypertrophic and so there are more motor neurons which innerve them.
Sexual dimorphism in human and canine spinal cord: role of early androgen 1986
- The sexually dimorphic nucleus (SDN) is in the medial preoptical area. In males is bigger due to the peak of testosterone during the critic period.
- Splenium of Corpus callosum and anterior commissure. Female neuronal fibers which link the two cerebral hemispheres are more than the male ones.
Physiologically, sex differences in the brain are those related to the amount of neurochemicals or neurotransmitters, or the intrinsic excitability of particular classes of neurons. In the adult there is considerable interest in the effects of estradiol on membrane excitability, receptor density, and levels of neurotransmitters.
Estradiol and the Developing Brain 2008
Effect of testosterone on SNC
During the first peak of testosterone the SNC is beginning to form. Most cells have the receptors for steroids. If testosterone is present, brain cells will start a differentiation in a dissimilar way from the differentiation of brain cells which are not exposed to it.
It is important to notice that male brain cells are different from female ones and this is due to the different karyotype. However the exposition to steroids makes dimorphism more marked.
Steroids modify cells in particular them structure. This action is significant, during the critic period which is restricted in time, and it is irreversible.
Testosterone makes a change of the dendrites disposition in some areas of the brain and so modifies the interaction among neurons. Infact the way of thinking is dimorphic!
Testosterone goes into hypothalamic cells and an enzyme called aromatase converts it into estradiol. Estradiol is derived from testosterone following aromatization of the A ring.
Estradiol binds his receptor and, as a consequence, receptors directly initiating the nuclear transcription of mRNA.
The estradiol actions can be divided along three lines:
- “classic” ER activation involving homodimerization, translocation to the nucleus and transcription;
- “nouveau” actions that still involve the nuclear receptor only acting in novel ways outside the nucleus;
- estradiol effects that apparently do not involve any receptor for estradiol but instead are mediated at other receptors, such as those for neurotransmitters.
Estradiol and the Developing Brain 2008
In females estradiol is bound by the alpha fetoprotein into the blood and so it leads to a lack of masculinization effect.
Malfunctions and consequences
In conclusion There are lots of cases in which this mechanism does not work properly or external causes change the differentiation in an irreversible way.
- Congenital Adrenal Hyperplasia (CAH). A mutation makes the adrenal glands produce more androgenic hormones. The increase of steroidogenesis of the mother or of the female fetus can change his developing. If the over production of androgen corresponds to the critic period the female fetus can be masculinized. Brain and uro-genital diaphragm get similar to male. Everything depends on the level of the hormone and on the time of exposition during the critic period.
- 5 Alpha Reductase Deficiency (5-ARD)
This enzyme converts testosterone into dihydrotestosterone. During the critic period this hormone binds testosterone receptor while testosterone peak decreases. So it is important for the differentiation of the uro genital diaphragm. At birth male will present an aspect very similar to female.
- Gender Identity Disorder (GID)
When for some reason during the brain differentiation something goes wrong there is a dissociation between the biological sex and the psychological one. These people are discontent with the biological sex they have. The only solution is to help them to transform their body into the opposite sex thanks to endocrinologists and surgeons.
