Estradiol Masculinizes Hypothalamus?

Pentti Degerstr|m trpede at
Thu Mar 21 13:13:02 EST 1996

I wrote: 

> Alpha-fetoprotein binds estrogen so only testosterone
> enters the cell (during critical period in pregnancy) and 
> is aromatized to estradiol after entering. Could defects 
> in this mechanism be the cause for homosexual behavior?

I feel safer to use a direct quote from James W. Kalat's 
book Biological Psychology (4th ed.): 

"According to studies on rodents, testosterone exerts a 
major part of its effect on the hypothalamus through a 
surprising route: After it enters a neuron, it is converted 
to estradiol!" ... "An enzyme found in brain can aromatize 
testosterone into estradiol." ... "Moreover, drugs that 
prevent testosterone from being aromatized to estradiol 
block the organizing effects of testosterone on sexual 
development. Apparently, androgens must be aromatized to 
estrogens to exert their organizing effects on the 
hypothalamus. Why, then, is the female not masculinized by 
her own estradiol? During the early critical period, 
immature mammals of most species have in their bloodstream a 
protein called alpha-fetoprotein, which is not present in 
adults (Gorski, 1980; Maclusky & Naftolin, 1981). 
Alpha-protein binds with estrogen and blocks it from leaving 
the bloodstream and entering cells that are developing in 
this early period. Nonrodents have additional mechanisms for 
inactivating estrogen; for example, it is likely that infant 
primates break down estrogens into inactive substances. In 
any event, testosterone is neither bound to 
alpha-fetoprotein nor metabolized; it is free to enter the 
cells, where enzymes convert it into estradiol. That is, 
testosterone is a way of getting estradiol into the cells 
when estradiol itself cannot leave the blood. This 
explanation of testosterone's effects enables us to make 
sense of an otherwise puzzling fact: Although normal amounts 
of estradiol have little effect on early development, an 
injection of a larger amount actually masculinizes a 
female's development. The reason is that normal amounts are 
bound to alpha-fetoprotein or metabolized, whereas a larger 
amount may exceed the body's capacity for inactivation; the 
excess is thus able to enter the cells and masculinize 
them."  pp. 428-429

"Ingeborg Ward (1972, 1977) exposed pregnant rats to a 
"stressful" experience during the final week of pregnancy 
.." "Such stress decreases brain levels of aromatase, the 
enzyme that converts testosterone into estradiol, which is 
necessary for masculinization of the hypothalamus (Weisz, 
Brown, & Ward, 1982). The stress caused the mothers to 
produce large amounts of adrenal hormones, which crossed 
into the fetuses' bloodstream and may have competitively 
inhibited the actions of testosterone. The stress also 
caused the male fetuses to produce their peak testosterone 
levels a day or two earlier than usual, before the critical 
period for brain differentiation (Ward & Weisz, 1980)." p. 

"Some pregnant women take the synthetic estrogen 
diethylstilbestrol (DES) to prevent miscarriage or to deal 
with other problems. DES can exert masculinizing effects 
similar to those of testosterone." p. 445

Harper's Biochemistry (23rd ed.): 
"A small percentage of testosterone is also converted into 
estradiol by aromatization, a reaction that is especially 
important in the brain, where these hormones help determine 
the sexual behavior of the animal." p. 545

I was also suggested to refer to works by John Money and the 
book, "The feminized brain" by Simon LeVay, and to Perkins, 
Fitzgerald & Moss (1995) (which I haven't done yet). Thank 
you, Larry S. and Jim K.


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