Nuclear Uptake of Estrogens in the Male Dove Hypothalamus: Relationship to Aromatase Activity and Behavioral Effects

Abstract

The natural estrogen, estradiol-17β, and a synthetic agonist, diethyl stilbestrol (DES), accumulated selectively in cell nuclei of the male dove preoptic area and posterior hypothalamus following intramuscular injection of the corresponding ³H-labelled tracers. Nuclear incorporation of radioactivity was saturable and specific, as shown by the effect of competition doses of unlabelled estrogens. The non-aromatizable androgen, 5α-dihydrotestosterone (DHT), did not compete with estrogens for nuclear binding sites, indicating that cross-reaction with androgen receptors is unlikely. Estradiol uptake was higher in the preoptic area than in the posterior hypothalamus, whereas DES uptake did not differ significantly between these areas. Although both brain areas are likely to contain specific estrogen receptors, only the preoptic area is known to be directly involved in the control of male precopulatory courtship behavior in the dove. Aromatase activity responsible for the local conversion of testosterone to biologically active estradiol-17β, measured in vitro, was also much higher in the preoptic and posterior hypothalamic areas than in adjacent areas of the basal forebrain and hypothalamus. The similarity in localization of aromatase activity and intranuclear uptake of estradiol indicates that the formation of estrogen may occur only within discrete brain areas containing specific estrogen receptors. Intranuclear uptake of DES in the preoptic area, which is half that of estradiol, is correlated with lower effectiveness both in inducing aromatase activity in the preoptic area and in eliciting an estrogen-dependent behavior in castrated males. The effectiveness of estrogens on behavior in the male dove is likely to depend upon characteristics of estrogen receptors in the preoptic area.

Formation of Behaviorally Active Estrogen in the Dove Brain: Induction of Preoptic Aromatase by Intracranial Testosterone

“…Conversion to E2 represented 0.4% of total radioactivity in POA. In contrast to results with in tramuscularly injected 5H-testosterone [45,46], polar me tabolites do not appear to be formed in large amounts from crystalline implants. Although testosterone was metabo lized rapidly (within 30 min of implantation), more than 80% of the total radioactivity in samples taken either 30 (fig.…”

“…Since there is negligible nuclear uptake of testosterone in AB [45,46], lack of effect is probably due to absence of receptors for testosterone or its metabolites. With the ex ception of LTI/TPL.…”

“…Al though metabolites of testosterone formed within the hypo thalamus appear to mediate some of the actions of an drogen on behavior [2,7,8,10,23], little is known of factors controlling their formation. However, examination of hor mone-dependent brain mechanisms underlying precopulatory behavior in the male ring dove (Streptopelia risoria) in dicates that steroid-metabolizing enzymes of the preoptic area (POA) have a regulatory role in determining the availa-concentrated in the POA [42j which is also the major target area for behavioral effects of E; [I I], and contains saturable E2 receptors [46], As levels of circulating E2 are low in the male [22], local production of E2 in the brain is likely to be an important regulatory step in the behavioral action of an drogen, particularly during transitions from aggressive to nest-orientated courtship in the initial stages of the repro ductive cycle [14,16].…”

Are separable aromatase systems involved in hormonal regulation of the male brain?

“…Stern, and McEwen, 1972). Concentration of estrogen has been demonstrated in vivu also by nuclear uptake of both 3H-E2 and 3H-DES, which binds specifically to ER in the brain (Steimer and Hutchison, 1985 ). Similarly, autoradiographic studies (MartineL-Vargas, Stumpf, and Sar.…”

“…The aromatase complex responsible for this intracellular conversion, probably comprising a specific form of cytochrome P-450 (Chen, Shively, Nakajin, Shinoda, and Hall, 1986), has been shown to occur in the adult (Callard, Petro and Ryan, 1978) and in the developing central nervous system of many vertebrate species Krohmer and Baum, 1989). Aromatase activity controlling estrogen availability is a crucial step for further cellular actions in the brain (Callard, Mak and Soloman, 1986;Hutchison and Steimer, 1984;Steimer and Hutchison, 1985).…”