How Hormones Shape Sexual Development

KEYPOINTS

• 01

  Biological sex develops in several layers

  Huberman separates chromosomal sex (XX, XY, and variants such as XXY and XYY), gonadal sex (testes or ovaries), hormonal sex, and morphological sex (the shape of the body and genitalia). Each is a separate step, and gender identity sits further along with major social influences. He asks listeners to set aside cultural meanings of 'masculine' and 'feminine' and focus on the biology.

• 02

  The Y chromosome works mainly by suppressing the female pathway

  Genes on the Y chromosome encode Müllerian inhibiting hormone, which blocks formation of the Müllerian ducts that would become female reproductive structures. Genes such as SRY drive testes formation. The placenta also produces hormones, and the mother's adrenal glands make testosterone, so a maternal tumor that secretes testosterone can partly masculinize an XX fetus, for example by enlarging the clitoris.

• 03

  Sex steroids act both quickly and slowly

  Testosterone and estrogen can signal at the cell surface within moments, including fast effects on the brain. Because they're fat-soluble, they can also pass through cell and nuclear membranes and switch genes on or off. These gene effects are what permanently shape tissues during development.

• 04

  DHT, not testosterone, builds the penis in the womb

  In the fetus, the enzyme 5-alpha reductase converts testosterone into dihydrotestosterone (DHT) in the genital tubercle, and DHT drives penis development, a primary sexual characteristic. At puberty, kisspeptin triggers GnRH and LH, the testes make testosterone, and testosterone drives secondary characteristics like a deeper voice, pubic hair and further genital growth.

• 05

  Estrogen, made from testosterone, masculinizes the brain

  Huberman repeats it deliberately: masculinization of the brain 'is not accomplished by testosterone.' Neurons containing aromatase convert testosterone into estrogen, and estrogen organizes the masculine circuits. He cites work from Nirao Shah's lab at Stanford showing that estrogen sets up masculine sexual and territorial behavior circuits, while testosterone later controls whether those behaviors are expressed. Estrogen that's too low also suppresses libido in males.

• 06

  Hormones only work if their receptors do

  In androgen insensitivity syndrome, a person is XY with internal testes that make testosterone, but the androgen receptor is mutated. They look and generally identify as female, and they often learn their karyotype only when they don't menstruate at puberty. They can't conceive because they have no uterus or ovaries. Huberman uses the condition to show that a hormone level alone tells you little without functioning receptors.

• 07

  Cannabis and alcohol push hormones toward estrogen

  Huberman says that all but one of the studies he found show cannabis raises aromatase activity. That's consistent with higher reported rates of gynecomastia in male users, and studies suggest use during pregnancy shifts fetal hormones in an estrogenic direction. Alcohol, especially beer and some grain alcohols, can also increase estrogenic activity, so he flags drinking during puberty as well as during pregnancy.

• 08

  Cell-phone radiation and the gonads: an emerging, uncertain literature

  A 2013 study that placed a phone under rat cages found small but significant defects in testicular and ovarian development. Many more studies have appeared since, in journals of mixed quality. One study (Eskander et al., Clinical Biochemistry) linked phone proximity and living near base stations with lower cortisol, thyroid hormones, prolactin and testosterone. Huberman cautions that confounders like nearby highways could explain such findings, and he's not aware of quality evidence that phones harm the brain.