estrone-sulfate and Neoplasms

Estrone sulfate (E

Topics: Biomarkers; Estrone; Gas Chromatography-Mass Spectrometry; Humans; Medical Laboratory Science; Neoplasms; Radioimmunoassay

Gynaecomastia is the most common disorder of the male breast. It can occur at any age, and for this reason laboratory investigations may be requested by clinicians from many specialties. Gynaecomastia may occur transiently in neonates. It may also occur transiently during puberty, when it is common and generally benign. It must, however, be regarded as unusual in prepubertal children and all young and middle-aged men. Although iatrogenic and benign gynaecomastia are common in the elderly, further investigations may still be justified since breast cancer or other neoplasm must be ruled out. Biochemical investigations, when warranted, are aimed at establishing an underlying cause. Endocrine investigations might include serum oestradiol (or oestrone if available), testosterone, luteinizing hormone, sex-hormone-binding globulin, human chorionic gonadotrophin, prolactin and thyroid function tests. In this review, the source and role of oestrogens in men, the androgen oestrogen dynamics, the causes and clinical entities of gynaecomastia, and interpretation of laboratory tests are described.

Topics: Androgens; Aromatase; Chorionic Gonadotropin; Endocrine Glands; Estradiol; Estrogens; Estrone; Gynecomastia; Humans; Male; Neoplasms; Prolactin; Sex Hormone-Binding Globulin; Testosterone

Transporter mRNA and protein expression data are used to extrapolate in vitro transporter kinetics to in vivo drug disposition predictions. Breast cancer resistance protein (BCRP) possesses broad substrate specificity; therefore, understanding BCRP expression-activity relationships are necessary for the translation to in vivo. Bidirectional transport of estrone-3-sulfate (E-3-S), a BCRP probe, was evaluated with respect to relative BCRP mRNA expression and absolute protein abundance in 10- and 29-day cultured Caco-2 cells. BCRP mRNA expression was quantified by real-time PCR against a housekeeper gene, Cyclophilin A. The BCRP protein abundance in total membrane fractions was quantified by targeted proteomics, and [(3)H]-E-3-S bidirectional transport was determined in the presence or absence of Ko143, a potent BCRP inhibitor. BCRP mRNA expression was 1.5-fold higher in 29- versus 10-day cultured cells (n = 3), whereas a 2.4-fold lower (p < 0.001) BCRP protein abundance was observed in 29- versus 10-day cultured cells (1.28 ± 0.33 and 3.06 ± 0.22 fmol/μg protein, n = 6, respectively). This correlated to a 2.45-fold lower (p < 0.01) efflux ratio for E-3-S in 29- versus 10-day cultured cells (8.97 ± 2.51 and 3.32 ± 0.66, n = 6, respectively). Caco-2 cell BCRP protein abundance, but not mRNA levels, correlates with BCRP activity, suggesting that extrapolation strategies incorporating BCRP protein abundance-activity relationships may be more successful.

Topics: ATP Binding Cassette Transporter, Subfamily G, Member 2; Biological Transport; Caco-2 Cells; Estrone; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Proteins; Neoplasms; RNA, Messenger

Topics: Breast; Breast Neoplasms; Estrogens; Estrone; Humans; Neoplasms