Estrone and Dehydroepiandrosterone Sulfatase Activities in Normal and Pathological Human Endometrium Biopsies

Abstract

The properties of estrone (E1) and dehydroepiandrosterone (DHEA) sulfatase activities are reported. Endometrial biopsy specimens were obtained using a Novak curette. Cycle stage was assessed from histological dating of endometrium, plasma estradiol and progesterone levels, and patient history. Both sulfatases are membrane-bound enzymes. The optimum pHs in Tris-HCl buffer were 6.5 for E1 sulfatase and 7.3 for DHEA sulfatase. Lowest activities and different optimum pHs were obtained with imidazole, maleate, or acetate buffers. DHEA sulfatase is more sensitive to thermal inactivation than E1 sulfatase. From kinetic studies, apparent Km values of 3.1 microM for E1 sulfatase and 5.7 microM for DHEA sulfatase were calculated. Noncompetitive inhibition of E1 sulfatase by DHEA sulfate and of DHEA sulfatase by E1 sulfate were demonstrated. The effects of inorganic ions and unconjugated steroids were also tested. These results are consistent with two different activities hydrolyzing E1 or DHEA sulfates. Neither activity varies during normal menstrual cycles nor is not correlated to plasma progesterone or 17 beta-estradiol levels. An isolated increase in E1 sulfatase occurred in the proliferative phase of irregular menstrual cycles, postantibiotic-treated salpingitis, or hyperplastic endometrium.

Enzymatic regulation of estradiol-17β concentrations in human breast cancer cells

“…This appears unlikely in the case of the human endometriurn; the activity of the enzyme is this tissue remained unchanged during the normal menstrual cycle, and was not correlated to plasma E 2 or progesterone levels [19].…”

“…The apparent K m values for these substx'ates were 6.3 gM and 14.9gM, respectively, in MCF-7 cells [17], and 6.8 gM and 14.9 gM, respectively, in human breast cancer tissue [18]. Whilst neither enzyme was subjected to product inhibition, DHEAS proved to be a potent inhibitor of estrogen sulfatase derived from MCF-7 cells (apparent K~ 0.6gM) [17], and also the enzyme derived from human endometrium [19]. Unlike estrogen sulfotransferase, estrogen sulfatase activity in human mammary cancer tissue is unrelated to ER status [7,18,20,21].…”

Tissue-specific transcripts of human steroid sulfatase are under control of estrogen signaling pathways in breast carcinoma

“…However, experimental evidence suggest the existence of tissuespecific STS isozyme(s) with different kinetic parameters for DHEAS and E1S [15][16][17]. Several studies demonstrate that STS enzyme activity and mRNA level are concordant [7,8,18], however the role of transcription factors, cis-acting elements, and the cellular context in STS regulation remain obscure.…”

Dehydroepiandrosterone sulphate sulphoydrolase from human placenta microsomes—Properties of the purified enzyme

“…The enzymatic conversion of DHEAS to DHEA by steroid sulphohydrolase appeared to play a crucial role in the metabolic road leading to the synthesis of androgens and estrogens. According to the literature DHEAS-ase activity measured both in animal and human showed sex, age and tissue variability [13,[17][18][19][20][21][22][23][24][25][26][27].…”

“…The concentration of DHEAS and DHEA, as well as sulphohydrolase activity exhibited differences in a variety of diseases [21][22][23][24][25][26][27].…”