Changes in Brain Aromatase and 5α-Reductase Activities Correlate Significantly with Seasonal Reproductive Cycles in Goldfish (Carassius auratus)*

Abstract

Aromatization and 5 alpha-reduction are known to be required for the full expression of testosterone actions in neuroendocrine tissues. Although aromatase and 5 alpha-reductase activities in brain and pituitary can be experimentally manipulated by castration and steroid replacement, naturally occurring variations during seasonal reproductive cycles have not been examined in any species. Goldfish (Carassius auratus) were selected for study because they exhibit exceptionally high levels of aromatase in both brain and pituitary, although 5 alpha-reductase levels resemble the vertebrate norm. Four animals of each sex were tested monthly through three breeding seasons (2.5 yr). Using previously validated techniques, the enzymes were assayed by product formation from [3H]androstenedione in homogenates of anterior hypothalamus-preoptic area (AHPOA), remaining telencephalon (TEL), whole pituitary, ovary, and testis. Seasonal variations in aromatase were most dramatic in the AHPOA of female fish, exhibiting a peak in April and May that was 6-fold higher than the nadir in July. As judged by changes in the appearance and weight of the gonads, maximal aromatase coincided with the spawning season, whereas low enzyme levels corresponded to reproductive inactivity. Seasonal variations were similar but of a lesser magnitude in the TEL of females and in the AHPOA and TEL of males (2- to 3-fold, peak to nadir). Both ovarian and testicular aromatase showed cyclic changes; however, activity was much lower than that in brain at all times of the year (4.5, 1.2, and 47.0 pmol/mg protein, maximal values in ovaries, testes, and AHPOA, respectively). Pituitary aromatase varied from 5-22 pmol/mg protein, but was not consistently correlated with season. Cyclic changes in 5 alpha-reductase were distinctly different from those in aromatase, with maximal values in both brain and pituitary occurring when fish were reproductively inactive. In general, circulating sex steroids were high when aromatase was high and low when reductase was maximal; however, there was no apparent causal relationship suggested by temporal changes in a given steroid. Variations in testosterone metabolism, by regulating the quantity and quality of active hormone in close proximity to receptor sites, may be responsible for the changes in feedback sensitivity and behavioral responsiveness that are known to occur in seasonal breeders.

Aromatase activity in the ovary and brain of the eastern mosquitofish (Gambusia holbrooki) exposed to paper mill effluent.

“…Although the data on androgen exposure and aromatase activity in fish are somewhat inconclusive [in one study, medaka (Oryzias latipes) treated with methyl testosterone exhibited decreased aromatase activity (63)], the exposure to environmental androgens is not inconsistent with increased aromatase activity. In some teleosts such as the goldfish (Carrasius auratus), there is an association between plasma levels of aromatizable androgen, brain aromatase activity, and aromatase mRNA at the beginning of the reproductive season (64). Further, goldfish treated with high doses of aromatizable androgen had increased plasma E 2 , supporting the relationship between increased plasma androgens and aromatase activity (65).…”

Profiling neuroendocrine gene expression changes following fadrozole-induced estrogen decline in the female goldfish

“…In goldfish, serum E2 levels exhibit a distinct seasonal profile with an increase around April and May, corresponding to the prespawning period (55). Accordingly, a similar seasonal profile for aromatase activity (42) and AroB expression (71) has been observed in the neuroendocrine brain Tel and Hyp. All these data indicate that the prespawning period from April to May is a critical period for physiological E2 action in neuroendocrine systems.…”

“…Since the signaling pathway activation will ultimately influence the transcriptional activities of downstream transcription factors including nERs, membrane actions of E2 provide another mode to regulate genomic gene expression (70). Fish are unique models in which to study E2 action because there is high activity of the B-subtype aromatase (AroB; the product of cyp19a1b), the enzyme responsible for synthesizing E2 from testosterone (T), in the neuroendocrine brain, telencephalon (Tel) and hypothalamus (Hyp) (42). Moreover, in contrast to mammals where aromatase and nER are commonly expressed in neurons, current studies in fish and birds strongly suggest that AroB is exclusively expressed in radial glial cells and nER is mostly expressed in neurons (16,43).…”

The Goldfish as a Model for Studying Neuroestrogen Synthesis, Localization, and Action in the Brain and Visual System

“…An association between neuroE synthesis and reproduction in goldfish is supported by studies showing that plasma levels of aromatizable androgen, brain Aro activity, and Aro mRNA all increase > 5-fold at the onset of seasonal reproductive activity and return to baseline in reproductively inactive fish (23). Seasonal (24)(25)(26).…”