SULFATION PATHWAYS: Formation and hydrolysis of sulfonated estrogens in the porcine testis and epididymis

Abstract

Boars exhibit high concentrations of sulfonated estrogens (SE) mainly originating from the testicular-epididymal compartment. Intriguingly, in porcine Leydig cells, sulfonation of estrogens is colocalized with aromatase and steroid sulfatase (STS), indicating that synthesis of unconjugated estrogens (UE), their sulfonation and hydrolysis of SE occur within the same cell type. So far in boars no plausible concept concerning the role of SE has been put forward. To obtain new information on SE formation and hydrolysis, the porcine testicular-epididymal compartment was screened for the expression of the estrogen-specific sulfotransferase SULT1E1 and STS applying real-time RT-qPCR, Western blot and immunohistochemistry. The epididymal head was identified as the major site of SULT1E1 expression, whereas in the testis, it was virtually undetectable. However, SE tissue concentrations are clearly consistent with the testis as the predominant site of estrogen sulfonation. Results from measurements of estrogen sulfotransferase activity indicate that in the epididymis, SULT1E1 is the relevant enzyme, whereas in the testis, estrogens are sulfonated by a different sulfotransferase with a considerably lower affinity. STS expression and activity was high in the testis (Leydig cells, rete testis epithelium) but also present throughout the epididymis. In the epididymis, SULT1E1 and STS were colocalized in the ductal epithelium, and there was evidence for their apocrine secretion into the ductal lumen. The results suggest that in porcine Leydig cells, SE may be produced as a reservoir to support the levels of bioactive UE via the sulfatase pathway during periods of low activity of the pulsatile testicular steroidogenesis.

Tissue steroid levels in response to reduced testicular estrogen synthesis in the male pig, Sus scrofa

“…However, homogenization of the frozen tissue in ice-cold methanol in the present study would be expected to denature these enzymes prior to significant conversion. The ratios of sulfated to free steroids in the present study are consistent with postharvest inhibition of sulfatase activity in the testis [30].…”

“…Sulfated steroids in tissues can be altered after tissue collection by sulfatase enzymatic activity [30]. However, homogenization of the frozen tissue in ice-cold methanol in the present study would be expected to denature these enzymes prior to significant conversion.…”

“…Letrozole administration uniquely affected endogenous C18 steroids in the testis, prostate, and liver, revealing tissue-specific regulation of estrogen synthesis and synthetic pathways. Testicular estrogens in the boar are primarily synthesized locally via aromatization of androgen precursors [27, 41, 43]; testicular estrogen sulfates result from subsequent local conjugation by sulfotransferases [27, 29, 30]. Letrozole inhibited testicular aromatase, resulting in the direct decrease in estrone and estradiol concentrations and an indirect decrease in the corresponding testicular sulfo-conjugate concentrations.…”

“…The potential roles of steroid sulfates, specifically DHEA-sulfate and estrogen sulfates, in steroid hormone production and distributions are intriguing, given the substantial amounts of sulfated steroid hormones in the boar [29, 30]. This study focuses on the interplay between free and conjugated steroid hormones in a tissue.…”

The potential disruption of estrogen and androgen homeostasis and adipocyte differentiation by metabolites of common airborne polychlorinated biphenyls

“…Our recent work has shown that the lower-chlorinated OH-PCB congeners 3, 8, 11, 25, and 52 can potently inhibit purified recombinant human SULT1E1 at nanomolar concentrations [61]. Sulfation of estradiol prevents its binding to estrogen receptors, thus terminating the estrogenic signal [156,157]. SULT1E1 inhibition, however, may cause the localized levels of active estradiol to increase and indirectly illicit estrogenic activity within tissues that express SULT1E1 without having an impact on circulating levels of estradiol [62].…”