A High Abundance Androgen Receptor in Goldfish Brain: Characteristics and Seasonal Changes*

Abstract

Testosterone (T) exerts its actions in brain directly via androgen receptors or, after aromatization to estradiol, via estrogen receptors. Brain aromatase activity in teleost fish is 100-1000 times greater than in mammals and would be expected to significantly reduce the quantity of androgen available for receptor binding. Experiments were carried out on the goldfish Carassius auratus to determine if androgen receptors are present in teleost brain and whether their physicochemical properties reflect elevated aromatase. Cytosolic and nuclear extracts were assayed with the use of [3H]T and charcoal, Sephadex LH-20, or DNA-cellulose chromatography to separate bound and free steroids. Binding activity was saturable and had an equally high affinity for T and 5 alpha-dihydrotestosterone (Kd, approximately 2.4 X 10(-9) M). Although mibolerone was a relatively weak competitor, the putative teleost androgen 11-ketotestosterone, methyltrienolone (R1881), estradiol, progesterone, and cortisol were poor ligands. Characteristics that distinguish this receptor from a steroid-binding protein in goldfish serum are the presence of binding activity in both nuclear and cytosolic extracts, a low rate of ligand-receptor dissociation, electrophoretic mobility, sedimentation properties in low vs. high salt, and tissue distribution (forebrain greater than or equal to pituitary greater than mid-/hindbrain). DNA cellulose-adhering and nonadhering forms were detected, but these did not differ in other variables measured. Although goldfish androgen receptors resembled those of mammals in all important physicochemical characteristics, they were unusually abundant (5-68 pmol/g tissue) compared to levels in rat brain, but comparable to levels in prostate and other male sex hormone target organs. Moreover, there were seasonal variations in total receptors, with a peak at spawning (April) 4- to 5-fold higher than values in reproductively inactive fish (July/August). This temporal pattern and magnitude of change corresponded to previously reported changes in brain aromatase. Thus, both phylogenetic and physiological correlates point to a functional interdependence between androgen receptors and aromatase in the brain. These studies in goldfish indicate that brain androgen receptors have a long evolutionary history and have been highly conserved through the vertebrate series.

Expression levels of sex hormone receptors in brains of Japanese medaka, <I>Oryzias latipes</I> (Actinopterygii: Beloniformes: Adrianichthyidae)

“…It is well known that androgen exerts its action in the brain directly via androgen receptors or via estrogen receptors after aromatisation to estrogen (Pasmanik and Callard 1988). In female fish, estrogen synthesis from androgen may be required to activate estrogen receptors.…”

Characterization of putative steroid receptors in the membrane, cytosol and nuclear fractions from the olfactory tissue of brown and rainbow trout

“…It is likely that such an effect will be mediated by specific androgen receptors. However, common to other intracellular androgen-binding sites identified in fish (Pottinger, 1987;Pasmanik and Callard, 1988), the olfactory tissue binding site has little affinity for 11-ketotestosterone, the (quantitatively) dominant androgen in male salmonids. Levels of 11-ketotestosterone in female salmonids are negligible compared to those in male fish (Scott et al, 1980) but levels of testosterone in female plasma during the reproductive period may exceed those in male fish by up to four-fold (Scott and Sumpter, 1983;Baynes and Scott, 1985 OHT, 11β-hydroxytestosterone; KT, 11-ketotestosterone; OHP, 17α-hydroxyprogesterone; DHP, 17α,20β-dihydroxy-4-pregnen-3-one; C, cortisol; E2, estradiol-17β.…”

“…Cytosolic and nuclear binding sites which display characteristics consistent with specific androgen receptors have been identified in a number of tissues in several species of fish, including brown trout skin (Pottinger, 1987(Pottinger, , 1988, goldfish brain (Pasmanik and Callard, 1988), and the electric organ of mormyrid fish (Bass et al, 1986). In skin and the electric organ the presence of androgen receptors has been linked to sexually dimorphic patterns of development, while androgen binding in the brain is suggestive of a behavioural role.…”

Social regulation of cortisol receptor gene expression

“…Astatotilapia burtoni has two androgen receptors (ARs), ARα and ARβ (Harbott et al, 2007). Astatotilapia burtoni ARα is part of the ARa/AR1 group in teleosts, which has been shown to have a higher affinity for testosterone than 11-ketotestosterone (Pasmanik and Callard, 1988;Pottinger, 1987;Slater et al, 1995). In contrast, ARβ has been shown to have a higher affinity for 11-ketotestosterone than testosterone in other fish (Olsson et al, 2005).…”