Distribution and steroid hormone regulation of aromatase mRNA expression in the forebrain of adult male and female rats: A cellular-level analysis using in situ hybridization

Abstract

Many of the effects of gonadal steroid hormones in the male brain are due to the actions of the testosterone metabolite estradiol, which is synthesized by the actions of the P450 enzyme aromatase. Aromatase activity is present in regions of the preoptic area, hypothalamus, and limbic system. Levels of aromatase activity in the brain are highly dependent on gonadal steroid hormones in many brain regions, but not all. We examined the distribution of aromatase mRNA in adult male and female rat brains as well as the regulation of the levels of aromatase mRNA in the brains of males by gonadal steroid hormones using in situ hybridization. This method was performed using a 35S-labelled cRNA probe, transcribed in vitro from the rat ovarian aromatase cDNA. In the adult male, many heavily labelled cells were found in the encapsulated bed nucleus of the stria terminalis (BNST), the medial preoptic nucleus (MPN), the ventromedial nucleus (VMN), the medial amygdala (mAMY), and the cortical amygdala (CoAMY). The regional distribution of aromatase mRNA was similar in females, but females tended to have a lower number of aromatase mRNA expressing cells in each region compared to males. Aromatase mRNA levels in the BNST, MPN, VMN, and mAMY tended to be lower in castrated males than in intact males, whereas aromatase mRNA levels were unaltered by castration in the CoAMY. The degree of reduction in mean levels of aromatase mRNA following castration does not simply account for the large changes measured in activity following castration. Examination of the entire population of individual cells expressing aromatase mRNA in castrated males suggests that aromatase mRNA may be regulated by steroid hormones differentially in specific populations of neurons within regions where activity is known to decrease following castration.

Sex-Dependent Regulation of Aromatase-Mediated Synaptic Plasticity in the Basolateral Amygdala

“…In addition, AROM expression has been reported in regions that are not directly involved in the regulation of reproductive behavior, such as the hippocampus (Wehrenberg et al, 2001;Hojo et al, 2004;Bender et al, 2010), the neocortex (MacLusky et al, 1994;Yague et al, 2006Yague et al, , 2008, and, as also shown here, the central and basolateral amygdala (Sanghera et al, 1991;Wagner and Morrell, 1996;Horvath et al, 1997;Roselli et al, 1998;. This suggests that the functions of AROM in the brain are not limited to reproduction, but extend to mood, affective behaviors, and memory formation.…”

“…In addition to the hippocampus, the amygdala is a brain region rich in AROM (Balthazart et al, 1991;Sanghera et al, 1991;Shinoda et al, 1994;Wagner and Morrell, 1996;Horvath et al, 1997;Roselli et al, 1998;. Anatomically, the amygdala comprises approximately a dozen nuclei that are developmentally derived from both pallial and subpallial sources (Swanson and Petrovich, 1998;Puelles et al, 2000;LeDoux, 2007).…”

Gonadal steroid hormone modulation of nociception, morphine antinociception and reproductive indices in male and female rats

“…The similar effects of T and E2 on basal nociception and morphine antinociception may be due to the aromatization of T to E2. Like male rats, females convert T to E2 via aromatase in the brain, though to a lesser extent than do males (Wagner and Morrell, 1996;Roselli and Resko, 1997). However, if the effects of T on basal nociception and morphine antinociception were actually due to E2, then the limited lordosis and uterine weights, and failure to show any proestrus or estrus stages based on vaginal cytology suggest that considerably less E2 is necessary to produce changes in nociception and morphine antinociception than is necessary to fully reinstate reproductive capabilities.…”

Androgen receptors are required for full masculinization of the ventromedial hypothalamus (VMH) in rats

“…The VMHvl and VMHdm contain high concentrations of steroid receptor mRNAs, and are the most studied of the four subdivisions (Simerly, et al, 1990;Wagner and Morrell, 1996). For example, the VMHdm appears to be critical for the expression of ultrasonic vocalization and scent marking behaviors in males (Yahr and Greene, 1992;Flanagan-Cato et al, 2001;Harding and McGinnis, 2005).…”