Essentials: How Hormones Shape Sexual Development

The episode, introduced by Andrew Huberman as a revisit of earlier material, sets out to explain hormones and how they lead to masculinization or feminization of the brain and body, with the stated aim of staying with "the biology, the physiology, the endocrinology, and the behavior." A hormone is defined as a chemical released in one part of the body, usually from a gland but sometimes from neurons, that travels and acts both on its source and on other organs and tissues.

That reach is what separates hormones from neurotransmitters, which tend to act more locally. The examples given of hormone-producing tissues are the thyroid, testes and ovaries, along with the closely linked hypothalamus and pituitary in the brain, which release hormones that trigger the release of still other hormones elsewhere in the body.

Hormone effects are sorted into fast and slow. Cortisol and adrenaline act quickly, while the sex steroid hormones, testosterone and estrogen, are lipophilic: they pass through the fatty membranes of the cell and the nuclear envelope and interact with DNA to control gene expression. Because of this, they can change what cells become and how they function over the long term, by promoting or repressing the expression of particular genes and the proteins they encode. The episode calls these steroid hormones "exceedingly powerful."

The development story begins with fertilization: sperm meets egg, the egg divides, and the resulting cells differentiate into skin, brain, muscle, fingers and the rest of the body plan. Hormones from both the mother and the developing fetus then influence whether the brain is "organized masculine or organized feminine." Listeners are asked to set aside cultural and psychological connotations of these terms, since the discussion is meant to be purely biological.

The first layer is chromosomal sex. Typically a person has two X chromosomes (traditionally described as female) or an X and a Y (who will become male), but the episode notes this is not always so: XXY and XYY configurations exist and have important biological and psychological impacts.

The second layer is gonadal sex: typically, though not always, testes are associated with males and ovaries with females. The Y chromosome drives this transition through specific genes. One encodes Mullerian-inhibiting hormone, which blocks formation of the Mullerian ducts, an important part of the female reproductive apparatus. Others, including SRY, promote formation of testes. The episode describes this as a fork in the road that happens very early, while the fetus is still an embryo.

Beyond that come hormonal sex, meaning the effects of estrogen, testosterone and their derivatives, and morphological sex, the shape of the body, including the genitalia and the jaw. The episode stresses that this "actually is quite complicated," and that it is "a long distance from chromosomes to gender identity," which has many social influences and is currently a dynamic area of public discussion. The episode does not go further into gender identity, focusing instead on the steps between chromosomes and body form.