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04/12: SEX DIFFERENCES IN THE BRAIN

Endocrine disruptorsAntiandrogen Propecia (finasteride) used for the treatment of male pattern hair

loss in adult men can cause abnormal sex development in male fetus.

DES (nonsteroidal estrogen) is given to women to prevent abortions; has

masculinizing properties in fetal females and feminizing properties in fetalmales. DES daughters have the same symptoms as CAH femalesDES sons have high incidence of hypospadius.

Agricultural pesticides (organochlorines) have estrogenic properties. They are

associated with an increased risk of urogenital malformations. Also an

increased risk of cryptorchidism in female gardeners sons, suggesting an

association with prenatal exposure to chemicals.

Herbicide atrazine is one of the most popular. Cause abnormal differentiation in

leopard frogs (R. pipiens).

Frogs 1. Live in the water and 2. Absorb chemicals through the skin. Are

especially sensitive to agricultural runoff.

Measured levels of atrazine and frog histology. Found oogenesis in frogtesticles and an increased number of testicular abnormalities (even atconcentrations that were more dilute than the suggested safe point).

A 46-day exposure to atrazine in mature male frogs caused testosterone to

plummet to the same level as a control female.

Exposure also caused more reproductive system abnormalities and general

abnormalities (e.g., extra limbs)Phytoestrogens, natural endocrine disrupters

Its possible that primates eat these as natural birth controlSoy is also high in phytoestrogens, and it is being proposed as a replacement

for regular milk in schools

Known to be antiestrogenic by their structural similarity and antiandrogenicby targeting 17B hydrogenase (prevents the conversion of

androstenedione into testosterone)

An increased amount of compound will increasingly inhibit the conversion of

androstenedione into testosterone.

Animals allowed to graze on alfalfa have increased sterility

May be useful in menopause and breast cancer; Asian women who eat a lot of

soy dont have high rates of breast cancer.

Current rise in levels in male infertility is linked to increased use of plastics. Up

to 12% of couples are sterile, 50% of which are attributed to men.

Sex is not entirely straightforward! A list of cases:

5E reductase deficiency in genetic male results in testes-at-12 syndromeCAH in genetic female produces phenotypic maleAI in genetic male produces phenotypic female

DES women, like CAH females, are phenotypic males

Endocrine disruptors in men may affect sexual reproductionPseudohermaphroditism in rhesus macaque

Hormonal effects on genital development:

XY + T inhibition = XX-like

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XX + T = XY-like

Rough/tumble play and mounting behaviors are organized by prenatal HExposure of XX to androgens produces incomplete male-like patters because this

is virilization without defeminization.

In rats

Conversion of T to DHT or E causes peripheral effects (activational)Castration has effects on penile sensitivity and intromission (activational)DHT and E synergistically restore full sexual behavior in castrates (activational)

Masculinization of SDN-POA is dependent on aromatization of T into E.

E fetal protein binds to maternal estrogen and prevents it from crossing the

blood-brain barrier.

Testosterone, however, has free circulation. Local conversion takes the extra

testosterone and converts it into additional E in the brain, which

promotes masculinization.

May also occur in primate brain.

T prevents F behavior (lordosis) in male via SDN-POA (defeminization)

(organizational)Bulbocavernosus muscle (erection production) is innervated by the spinal cord

nucleus SNB which is sexually dimorphic. SNB is present in both sexes at

birth, but disappears selectively in females. Testosterone inhibitsdisappearance and thus promotes maintenance.

Thus T promotes M behavior (erection) via SNB.Implications

The complete pattern of ejaculatory behavior in rats depends on both

organizational (brain/SDN) and activational (body/SNB) effects of H.

M & F are similar in that sexual motivation and sexual performance are

organized separately in the nervous system.

Neural and endocrine bases of proceptive behavior (mounting, patting) aredifferent from receptive behavior (lordosis).

Hormonal regulation of behavior

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sociality is neither organizational nor activational but may be influenced by

hormones.Giving adult female rhesus testosterone will cause yawning; thus yawning has

only an activational basis.

Summary of concepts

Secretions from the testes produce masculinization and defeminization innormal males

Masculinization and defeminization are separate processes

Complete behavioral differentiation requires changes to both reproductive

anatomy and CNS structures

Across species, females can be masculinized by aromatizable androgens (theory

of mammalian sexual differentiation)

Organizational effects of nonaromatizable androgens (DHT) are species specific

Organizational effects of hormones alter adult sensitivity to activational effects

of hormones.

Autoradiography studies

Tissues are injected with radioactively labeled hormones, which selectivelyconcentrates in target tissues with receptors.

An X-ray sensitive emulsion reveals where binding occurs.

Androgen/estrogen/progestin sensitive cells are most abundant around the

ventricles, particularly in the hypothalamus, amygdala, and hippocampus

Amygdala is the most sexually dimorphic part of the brain in humans. Castration

of a male induces a 30% shrinkage. Its size is positively correlated withaggression. It controls aggression, fear, and pleasure.

In the male brain, the pattern of sex steroid receptors is conserved from rats toprimates. What differs is the location of steroid metabolizing enzymes.

Lesions of the mPOA disrupts copulation but not erection, masturbation, or

ejaculation. Presentation of stimulus will result in behaviorRemote electrical stimulation of the mPOA in males causes erection and

mounting.

The mPOA integrates internal and external environments and ultimately

expresses the final stages of mating behavior.

Nature vs Nurture in humans

Nurture: infants are psychosexually neutral at birth and individuals can choose

their gender identity

Nature: prenatal exposure to hormones influences all aspects of identity; nature

has nothing to do with it.

Alternatively: adult identity is a mixture of biological basis and social history

The Money twinsIn which a twin male was accidentally castrated and then raised as a girl after

being given an artificial vagina. Prepuberty, Money claimed it as proof ofNurture hypothesis. After puberty, the twin exhibited gender dysphoria

and eventually opted for a sex change, later married, then committed

suicide.Thus you cannot change your biological sex (organizational hormones are

permanent)

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Although sex is a continuum not a dichotomy.