Regulation of Brain Aromatase Activity in Rats*

Abstract

We studied the distribution and regulation of aromatase activity in the adult rat brain with a sensitive in vitro assay that measures the amount of 3H2O formed during the conversion of [1 beta-3H]androstenedione to estrone. The rate of aromatase activity in the hypothalamus-preoptic area (HPOA) was linear with time up to 1 h, and with tissue concentrations up to 5 mgeq/200 microliters incubation mixture. The enzyme demonstrated a pH optimum of 7.4 and an apparent Michaelis-Menten constant (Km) of 0.04 microns. We found the greatest amount of aromatase activity in amygdala and HPOA from intact male rats. The hippocampus, midbrain tegmentum, cerebral cortex, cerebellum, and anterior pituitary all contained negligible enzymatic activity. Castration produced a significant decrease in aromatase activity in the HPOA (P less than 0.001), but not in the amygdala or cerebral cortex (P greater than 0.05). The HPOAs of male rats contained significantly greater aromatase activity than the HPOAs of female rats. In females, this enzyme activity did not change during the estrous cycle or after ovariectomy. Administration of testosterone to gonadectomized male and female rats significantly enhanced HPOA aromatase activities (P less than 0.05) to levels approximating those found in HPOA from intact males. Therefore, our results suggest that testosterone, or one of its metabolites, is a major steroidal regulator of HPOA aromatase activity in rats.

Androgen Metabolism in the Brain of the Green Anole Lizard (Anolis carolinensis): Effects of Sex and Season

“…The different patterns in the regulation of aromatase and 5␣-reductase are mainly due to T sensitivity. That is, studies of birds (Schumacher and Balthazart, 1986;Steimer and Hutchison, 1990) and mammals (Reddy et al, 1973;Roselli et al, 1984Roselli et al, , 1985Steimer and Hutchison, 1990; Sample sizes (n) are given in parentheses. For assays of brainstem and "rest of brain" (forebrain, optic tectum, cerebellum), sample size is the number of pools, in which each pool consisted of tissue from two animals of the same sex.…”

Cellular mechanisms of estradiol-mediated masculinization of the brain

“…One of the surprises was that treatment of neonatal females with exogenous estradiol, originally administered as a control for testosterone, also induced complete masculinization of brain and behavior [10,11]. We now understand that most sexually dimorphic areas of the brain contain substantial levels of both aromatase cytochrome P450 (CYP19), the enzyme responsible for the conversion of testosterone to estradiol, and high densities of estrogen receptors [12][13][14][15][16][17]. Maternal estrogens are sequestered in the peripheral circulation of the fetus by alphafetoprotein, a steroid-binding glycoprotein that has high affinity for estradiol but little affinity for androgens, allowing the testicular testosterone to reach and influence fetal target tissues, including the brain.…”

Rapid effects of aromatase inhibition on male reproductive behaviors in Japanese quail

“…It is generally thought that brain aromatase activity is controlled by steroids that act essentially by enhancing the transcription of the aromatase gene and thus the concentration of the enzymatic protein (Abdelgadir, Resko, Ojeda, Lephart, McPhaul, and Roselli, 1994;Balthazart and Foidart, 1993;Hutchison, Steimer, and Hutchison, 1986;Roselli, Abdelgadir, and Resko, 1997;Roselli, Ellinwood, and Resko, 1984;Roselli, Horton, and Resko, 1987;Roselli and Resko, 2001;Steimer and Hutchison, 1981). In addition, it has also recently become clear that aromatase activity can be rapidly (within min) modulated by calcium-dependent phosphorylation processes that completely block enzyme activity (Balthazart et al, 2001a;Balthazart et al, 2001b).…”