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Introduction

Neural masculinization is a developmental process by which the expression of male behavior is affected by androgens during the perinatal sensitive period. Genitalia are fully masculinized only if they are exposed to androgen at an early stage in development. It is thought that the same steroidal signals that masculinize the structure and development of genitalia are also responsible for masculinizing behavior. Masculinization is also thought to be influenced by genetics. Hormones have “organizational and activational” effects on neural structure. Hormones act on the nervous system and modify neural development. The organizational hypothesis states that the actions of hormones in the development process alter tissue differentiation. This process begins before one is born. The level of lordosis and intromissions, sexual behaviors that differentiate females from males, are important aspects in discovering to what extent a male or female’s nervous system has been masculinized.

Where Masculinization Occurs

Steroid hormones are essential in the masculinization of two regions of the central nervous system: the spinal nucleus of the bulbocavernosus (SNB) and the posterodorsal aspect of the medial amygdala (MePD).

SNB

Testosterone is present to stop cell death of motoneurons and their target muscles during the perinatal period. Masculinization of this area is caused by the activation of androgen receptors.

• Perinatal androgen permanently changes the number of neurons in the spinal cord.
• There is a sensitive period of androgenic masculinization. Androgen must arrive before the muscles and motoneurons have died or else androgen will not have an effect on masculinization.

MePD

• Testosterone causes masculinization of MePD even in adulthood. Thus, steroids affect sexual differentiation of this system through many different stages of development. The masculinization of neural structure is affected by estrogen and androgen receptors

Testosterone

Testosterone is taken up by the brain cells where it is converted into estrogen by the enzyme aromatase . Testosterone is a steroid hormone found in the testes of males and the adrenal cortex of both sexes and is a critical hormone in the masculinization process that activates androgen, a sex hormone in males. Females have very little testosterone, causing the neurons to develop along a “female pathway” . Yet, if they do overproduce testosterone, females experience an increase in masculine behavior that results in a change within their nervous systems.

Estrogen

Estrogen acts on estrogen receptors to propagate a chain of events, including the activation of certain genes in the cell nucleus. Estrogen causes masculinization in males and feminization in females. Females do not experience this process because they have a blood enzyme that binds to estrogen and prevents it from crossing the blood-brain barrier. Although mothers do produce estrogen that goes to the bloodstream of the fetus, alpha-fetaprotein binds to estrogen and inhibits it from entering the brain. If there is too much estrogen, this protein will not have enough receptors to inhibit it, resulting in the masculinization of the fetus.

Diseases Related to Masculinization

Adrenogenital Syndrome

A disease that affects females that is caused by an over production of androgens in the adrenal gland during the prenatal period. AGS generates a partial masculinization of the female genitalia, which causes long-term behavioral differences, including higher than normal energy levels, along with aggression.

Congenital Adrenal Hyperplasia

A disease in which the people affected lack an enzyme in the adrenal gland that the body needs to produce hormones such as cortisol and aldosterone. In response, the body producs more androgen, causing the person affected by the disease (male or female) to display increased male characteristics .

Effects of Masculinization

In order to increase muscle-building and masculinizing effects, anabolic steroids are often utilized. Steroids can affect neuronal myelination, migrational patterns, growth, proliferation, death of cells, and dendritic growth . A variation in types of steroids and relative concentrations creates many complex differences between the sexes. There are also social implications to masculinization. Although men and women do contain differences in their genetic makeup, uncovering more information about masculinization could lead to more defined separations between the sexes. These separations are critical in understanding the interconnections between behavior and genetics, especially when focusing on which gender characteristics are innate and which ones are garnered from experience and the environment

Neural Masculinization