8.5 Sexuality and Hormones

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5. Hormones, Sex and Gender - Update 25 Aug. 2021. 

Few words are more loaded with meaning than the word "sex." Sexual activity is a biological imperative and a major human preoccupation. The physical differences between men and women that underlie partner recognition and reproduction are obvious. In contrast, our understanding of the bases of the behavioral differences between the sexes is not as good. In many cases their very existence remains controversial, e.g., basic differences between male and female have been called into question by feminists,  homosexuals, and transgenders.

Without hormones, no sexuality! But hormones do not determine preference, they supply drive and make preference possible. Preference is determined by sex chromosome/sex hormone brain patterning; by early childhood interactions; by social learning, tradition, culture, peer group and parents; and nowadays by the Media. The complex reality is just the opposite of the simplistic "born gay" idea that presently fuels homosexualism. If you look at the big picture of what makes a person sexual: the sex chromosome/sex hormone is the part underlying external appearance/gender behavior and degree of lust but the social influence shapes it into preference and specific behavior.

   The male hormone Testosterone (TE) and the female hormone Estrogen estradiol (E2) are chemically nearly identical. Both are made in men and women; and in the synthesizing process TE is the next step from E2. The TE is a ‘masculinizing’ hormone; its effects on the sexually neuter fetus (3-4 months shows no external sign of gender) is to make it develop in the male direction. Before puberty, both boy and girl have low levels of TE and E2, and sexual responsiveness is low. Puberty in a boy is due to activation of his testes from the rising brain pituitary hormones, FSH and LH, to produce male adult levels of TE. Because of it, a boy masculinizes (increases muscle mass, develops typical sexual pattern body hair, aggressive sexuality and pressure for orgasm). A girl's ovaries respond to the same stimulus by producing E2 with block to TE.
   Testosterone determines the drive in man and woman. A castrated male has no sexual desire and no ability to get erection unless he is injected with TE, right after which he feels desire, can get erection and can have orgasm. Young men are more sexually aggressive than young women in keeping with their higher TE but by middle age a menopausal woman may experience an increased desire under the stimulus of rising FSH and LH causing the adrenal glands and the ovaries to produce more TE and less E2. And the universal decline in sexuality in old age, seen unevenly but ultimately in a man or woman who lives long enough, is due to the very low TE in old men and old women.

More about TEstosterone and sexuality: its stimulation of sexual responsiveness in women is achieved by rather low levels. Young men have 10 to 15 times higher TE blood levels than young women, but even the low TE in the women is important for sexuality because when there is very, very low or no TE, the female has no lust. The production of male hormones (TE and like-acting) by the glands of the adrenal cortex explains the continuation of sexuality in women whose ovaries are removed or have lost function.

   So we are sexual animals roughly based on each one’s TE blood level. If its source is removed we stop sexuality. And when we get TE overproduced in a tumor or overdosed because of androgen sports steroids, we may become hypersexual.

   Hypersexual behavior is typified by its causing the aggressive seeking out of orgasm with others or inanimate objects at the expense of social conventions. When a man or a woman gets overdosed with androgen (TE, et al), hypersexuality may result but women are more sensitive to the affect.

   Understanding the above can be important in making a diagnosis. When a previously sexually un-aggressive woman starts sexually molesting men or women, it may be a sign she is developing a TE-producing tumor or taking androgen steroids for sports.

   Knowledge of the importance of the hormone levels and its affects should make us less punishing of the sexual behavior of those who are experiencing sharply rising TE blood level, e.g., teenage boys. They have a problem controlling sexuality. I do not suggest they should be forgiven for causing injury but when it is only a question of touching, groping or obscene proposal, I think it should be treated with humorous, educational  understanding balanced by concern for the woman who may be sexually mishandled.

   I have focused on TE but what about estrogen E2? It acts as anti-male hormone; it opposes the TE effect. When E2 is given to a man he becomes less sexually aggressive and may lose his lust. It is possible that E2 has subtle effects that make for typical female sexuality such as a more gentle approach to seeking sex.

   I should not leave readers with an idea that blood and tissue level of hormone are the only internal determinant of sexuality. We have come to understand that all hormones work by combining with surface receptors on the target cell and that the numbers of receptors determine the sensitivity to the affect of a hormone. For example, if a person’s cells lack receptors for TE, that person can produce (or be dosed with) huge amounts of TE without its having any affect. There is a genetic disease, testicular feminization, where the victim is born a genetic male with xy chromosome pair and with abdominal testes and producing abnormally high level of TE yet because he has no receptors he develops physically as a typical woman with vagina but no uterus, and with testes in the abdomen where the ovaries should be. Such ‘men’ have nice female breasts and they function well as attractive women until after marriage when they come complaining of inability to get pregnant. They can easily be shown to be chromosomally male by their sex chromosomes and biologically not female by the absent uterus and by the abdominal testes and high TE blood levels. This should make for a more sympathetic understanding of transsexualism (desire to function as opposite sex, usually men wanting to be women) and transvestism (desire to dress like the opposite sex). At times these are psychologically based conditions but, regardless of cause, we cannot help having greater sympathy for these persons when we contemplate testicular feminization and try to answer the question “What is a man?” And “What is a woman?”

But what is the mechanism of the hormonal affects on sex determination and gender identification? 
(The below technical description may be skipped by uninterested readers)

Human males and females have a complement of 23 chromosomal pairs, and only one pair shows difference between the sexes. Females have this pair showing X chromosomes (and are therefore "XX"), whereas males show one copy of the X chromosome paired with a Y chromosome (XY). The other 22 pairs of non sex chromosomes are the autosomes. Some genetic gender-ID determinants arise from the presence of a Y chromosome, but other determinants arise from sex-specific patterns of the autosomal gene expression that exert their impact during development.

How do differences in genes and gene expression make the differences between the brains of men and women? The key intermediates are the sex hormones -  testosterone and estrogen. These hormones act in the embryo as well as after, first organizing the physical development of both genitalia and brain regions, and later activating particular physiological and behavioral responses. Hormonal regulation is especially complex because the nervous system, which is influenced by sex steroids, also controls their synthesis. This feedback loop may help to explain how the external environment, including social and cultural factors, can help shape sexual dimorphism (the physical differences between men and women) at a neural level.

What are the crucial neural differences that underlie sexually dimorphic behaviors? Clear physical and molecular differences between the brains of men and women have been found. These differences imply that neural circuitry differs between the sexes, and in a few cases these distinctions in connectivity may be directly related to behavioral differences. In other cases, however, sexually dimorphic behaviors appear to result from differential usage of the same basic circuits.

Before proceeding we must define the usage of two words that are commonly confused with each other: sex and gender. As a descriptor of biological differences between men and women, the word sex is used in three ways. First, anatomical sex refers to overt differences including the differences in the external genitalia as well as other sexual characteristics such as the distribution of body hair. Gonadal sex refers to the presence of male or female gonads - the testes or ovaries. Finally, chromosomal sex refers to the distribution of the sex chromosomes between females (XX) and males (XY).

Whereas sex is a biological term, gender encompasses the collection of social behaviors and mental states that typically differ between males and females. Gender role is the set of behaviors and social mannerisms that is typically distributed in a sexually dimorphic fashion within the population. Toy preferences in children as well as distinctive attire are some examples of gender roles that can distinguish males from females. Gender identity is the feeling of belonging to the category of the male or female sex. Importantly, gender identity is distinct from sexual orientation, the erotic responsiveness displayed toward members of one or the other sex.

Are gender and sexual orientation genetically determined? Or are they social constructs molded by cultural expectations and personal experience? As the examples in this chapter will illustrate, we are still far from untangling the contributions of genes and environment to such complex phenomena. However, our recognition that genes and experience interact to shape neural circuits gives us a more realistic framework with which to answer this question compared to our predecessors, who were constrained by the simplistic view that genes and experience acted in mutually exclusive ways.

The role of the SRY gene in sex determination in humans.

SRY, the sex-determining locus (in below figure the dark blue domain), resides on the nonhomologous region of the short arm of the male Y chromosome. The presence of SRY is determinative for male differentiation in many mammals, including primates and most rodents. Normally an X- or Y-bearing spermatozoon fertilizes an oocyte to generate XX females or XY males sperm, and the resulting phenotypic sex is concordant for the chromosomal sex. Rarely SRY translocates to the X chromosome or an autosome (not shown). In such cases XX^SRY offspring are phenotypically male while XY^ΔSRY offspring (the Δ indicating a gene deletion) are phenotypically female.

How does SRY instruct the undifferentiated gonads to develop into testes? The female differentiation program appears to be the default mode; patterning genes prime the body and gonads to develop along female-specific pathways. The SRY gene encodes a transcription factor that induces expression of genes, some of which prevent execution of the default program and initiate the process of male gonadal differentiation. One of the best-studied targets of the SRY transcription factor is another transcription factor, SOX9, which is required for differentiation of the testes. SOX9 in turn activates a variety of genes required for formation of testicular Sertoli cells. Thus SRY initiates a cascade of inductive interactions that ultimately lead to male-specific gonad development.

And from that point, the gonads synthesize hormones that promote sexual differentiation.

The chromosomal complement of the embryo directs sexual differentiation of the gonads and in turn the gonads determine the sex-specific features of the nervous system and the rest of the body. They do this by secreting hormones. Gonadal hormones have two major roles. Their developmental role is traditionally referred to as organizational because the early effects of hormones on the brain and the rest of the body lead to major, generally irreversible, aspects of cell and tissue differentiation. Later some of the same hormones trigger physiological or behavioral responses. These influences, generally termed activational, are reversible.

One example of an organizational role of gonadal hormones is seen in the differentiation of structures that connect the gonads to the external genitalia. In males the Wolffian duct gives rise to the vas deferens, the seminal vesicles, and the epididymis. In females the Müllerian duct differentiates into the oviduct, the uterus, and the vagina (Figure 2, paragraphs below). Initially both female (XX) and male (XY) embryos possess Wolffian and Müllerian ducts. In males the developing testes secrete a protein hormone, the Müllerian inhibiting substance (MIS), and another hormone, testosterone. MIS leads to a regression of the Müllerian duct and testosterone induces the Wolffian duct to differentiate into its mature derivatives. In females the absence of MIS permits the Müllerian duct to differentiate into its adult derivatives, and the absence of circulating testosterone causes the Wolffian duct to resorb. Thus the Y chromosome overrides a female default program to generate male gonads, which in turn secrete hormones that override a female default program of genital differentiation.

Sexual differentiation of the internal genitalia.

Embryos of both sexes develop bilateral genital ridges (the gonadal anlagen) that can differentiate into either testes or ovaries; then the Müllerian ducts, which can differentiate into oviducts, the uterus and the upper vagina; and also Wolffian ducts, which can differentiate into the epididymis, the vas deferens, and the seminal vesicles. In XY embryos the expression of the SRY gene in the genital ridge induces differentiation of this tissue into testes and differentiation of the Wolffian ducts into the rest of the male internal genitalia, while the Müllerian ducts are resorbed. In XX embryos the absence of SRY permits the genital ridges to develop into ovaries and the Müllerian ducts to differentiate into the rest of the female internal genitalia; in the absence of circulating testosterone the Wolffian ducts degenerate. (MIS, Müllerian inhibiting substance.)

(Rejoin text after the skipping) Getting back to "What is a man?" and "What is a woman?", for the average person who does not know the internal details of the above development it is the outward appearances that count. These suggest a woman is a woman and a man is a man to the extent their appearance (and more recently the direction of their sexual orientation based on outer behavior) accords with our perception of what is womanly or manly rather than her/his X or Y chromosomes or ovaries or testes. From that follows the massively simplistic "I was born gay" and the effective argument "so treat me as a 3rd sex or even a separate race with the inalienable human right to be given a place in accepted society separate from the old fashion man/woman dichotomy". And from that follows the present legal status that decrees gay marriage and even transgender separate bathroom rights.

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