Sexual Differentiation Berthold’s Experiment (1849) Arnold Adolph Berthold (1803-1861) University of Göttingen Germany Bob the Chicken

Organizational and activational effects of steroids Organizational: To guide the organization of brain, endocrine glands, and behavior during hormone-sensitive “critical periods” or epochs of fetal and postnatal life. Activational: At puberty and afterward, to generate the growth of secondary sex characteristics, to activate endocrine systems involved in sperm and egg production, to mature neuroendocrine systems required for pregnancy, and to stimulate the appropriate “adult” behaviors required for those functions. Masculinization: Active process of acquiring “male-typical” anatomy, physiology, and behavioral functions. Demasculinization: Active process of losing “male-typical” functions. Feminization: Default or “passive” process in mammals of acquiring “female-typical” anatomy, physiology, and behavioral functions. Defeminization: Active process of losing “female-typical” functions.

Genetic → Hormonal differentiation

Internal differentiation

External differentiation

Brain differentiation (pre and postnatal) (Sexually dimorphic nucleus of the medial preoptic area) Male Female TP-treated Castrated Female Male

Differentiation of spinal cord (Spinal nucleus of the bulbocavernosus muscle) Castrated male TP-treated female Female Male

Sexual differentiation requires Prostaglandin E2 in hypothalamus Margaret M. McCarthy (1957 - ) University of Maryland Baltimore Discovered that COX-2 inhibitors disrupted formation of SDNs in males. Also disrupted display of masculine sexual behavior after puberty. Effects irreversible. Replacement with PGE2 in perinatally castrated males could restore both growth of SDNs and masculine sexual behavior.

(with conversion to estradiol in mammals, and functional activation of prostaglandin E2!)