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

Abstract

Production of steroid hormones is complex and dependent upon steroidogenic enzymes, cofactors, receptors, and transporters expressed within a tissue. Collectively, these factors create an environment for tissue-specific steroid hormone profiles and potentially tissue-specific responses to drug administration. Our objective was to assess steroid production, including sulfated steroid metabolites in the boar testis, prostate, and liver following inhibition of aromatase, the enzyme that converts androgen precursors to estrogens. Boars were treated with the aromatase inhibitor, letrozole from 11 to 16 weeks of age and littermate boars received the canola oil vehicle. Steroid profiles were evaluated in testes, prostate, and livers of 16, 20, and 40 week old boars using liquid chromatography/mass spectrometry. Testis, prostate, and liver had unique steroid profiles in vehicle-treated animals. Only C18 steroid hormones were altered by treatment with the aromatase inhibitor, letrozole; no significant differences were detected in any of the C19 or C21 steroids evaluated. Testis was the only tissue with significantly decreased free estrogens following treatment with the aromatase inhibitor; estrone and estradiol concentrations were lower (p < 0.05) in testes from 16, 20, and 40 week letrozole-treated boars. However, concentrations of the sulfated conjugates, estrone-sulfate and estradiol-sulfate, were significantly decreased (p<0.05) in 16 and 20 week boar testes, prostates, and livers from letrozole-treated boars. Hence, the distribution of estrogens between the free and conjugated forms was altered in a tissue-specific manner following inhibition of aromatase. The results suggest sulfated testicular estrogens are important estrogen precursors for the prostate, potentially enabling peripheral target tissues to synthesize free estrogens in the male pig.

Expression of CSF1, AR, and SRD5A2 during Postnatal Development of the Boar Reproductive Tract

“…The SRD5A2 in the prostate is key to the local conversion of testosterone to DHT, a particularly potent androgen involved in the maintenance of prostate function. Local activity of the SRD5A2 enzyme, coupled with local conversion of testosterone sulfate to testosterone [ 69 , 70 , 71 ], suggests local androgenic signaling independent of fluctuations in peripheral testosterone. The importance of SRD5A2 to prostatic development in humans and laboratory rodents is demonstrated by the small and undeveloped prostates present when a mutation in the gene prevents expression of a functional enzyme [ 14 , 72 ].…”

Gene Expression in Porcine Bulbourethral Glands

“…Letrozole treatment rapidly reduces circulating estrogen levels [4], as illustrated in Figure 1. Treatment and results from other analyses of all of these animals, including steroid levels, were previously described and indicated that letrozole treatment dramatically reduced estrogen synthesis as expected [9][10][11][12].…”

“…Bulbourethral glands were collected from littermate pairs of boars at the following postnatal ages: early juvenile 2 weeks (n = 2 treatment, n = 2 control), juvenile 6.5 weeks (n = 4 treatment, n = 4 control), early puberal 16 weeks (n = 6 treatment, n = 6 control), and postpuberal 40 weeks (n = 2 treatment, n = 2 control) [9][10][11][12]. Ages were chosen to represent physiological states and apparent transition points in control animals.…”

Do Dehydroepiandrosterone (DHEA) and Its Sulfate (DHEAS) Play a Role in the Stress Response in Domestic Animals?

“…Among domestic mammals, the male pig shows the higher circulating DHEAS concentrations (13). However, SULT2A1 and SULT2B1 are poorly expressed in the boar adrenals in comparison with testes (36), and available data suggest that DHEA sulfonation occurs mainly in testicles and epididymis (36)(37)(38)(39)(40). DHEAS is undetectable in plasma of nonpregnant gilts (37) and in the adrenal of adult cycling sows (19).…”