Uptake and Concentration of Steroid Hormones in Mammary Tissues

Abstract

In order to exert their biological effects, steroid hormones must enter the cells of target tissues and after binding to specific receptor molecules must remain for a prolonged period of time in the nucleus. Therefore the endogenous levels and the subcellular distribution of estradiol, estrone, DHEAS, DHEA ad 5-Adiol were measured in normal breast tissues and in malignant and nonmalignant breast tumors from pre- and postmenopausal women. For estradiol the highest tissue levels were found in the malignant samples. No differences were seen in these levels between pre- and postmenopausal women despite the largely different peripheral blood levels. For estrone no differences were found between the tissues studied. Although the estradiol concentration was higher in the estradiol-receptor-positive than in the receptor-negative tumors, no correlation was calculated between the estradiol and the receptor consent. Striking differences were seen between the breast and uterine tissues for the total tissue concentration of estradiol, the ratio between estradiol and estrone, and the subcellular distribution of both estrogens. At similar receptor concentrations in the tissues these differences cannot easily be explained. Regarding the androgens, the tissue/plasma gradient was higher for DHEA than for 5-Adiol, and for DHEAS there was very probably a much lower tissue gradient. The highly significant correlation between the androgens suggests an intracellular metabolism of DHEAS to DHEA and 5-Adiol. Lower concentrations of DHEAS and DHEA were observed in the malignant tissues compared with the normal ones and the benign lesions. For 5-Adiol no differences were found and therefore these data do not support our original hypothesis on the role of this androgen in the etiology of breast abnormalities. Hence the way in which adrenal androgens express their influence on the breast cells remains unclear.

Patterns of Sex Steroid Hormones in Nipple Aspirate Fluid during the Menstrual Cycle and after Menopause in Relation to Serum Concentrations

“…This delay in the peak concentrations of the estrogens explains the previously observed lack of correlation between serum and NAF estradiol (1, 2), which is seen again in the present study, and has been observed between serum and tissue concentrations of estradiol by others (3,5,11). However, the association between serum progesterone and NAF hormones has not been examined previously in detail.…”

The local hormonal environment and related biomarkers in the normal breast

“…In a second study of 47 women the serum estradiol concentration at mid-luteal phase was similar (356t65.4 pmol/l), whereas in NAF it was lower (484t28 pmol/l) (Chatterton et al 2004). The latter value corresponds closely to concentrations of estradiol in tissue of premenopausal women when the tissue concentration is expressed in pmol/g (Thijssen et al 1986, Blankenstein et al 1999. There was no correlation between concentrations of DHEAS and ES in serum and those in NAF.…”

Estrogen mediates Aurora-A overexpression, centrosome amplification, chromosomal instability, and breast cancer in female ACI rats

“…In premenopausal women, however, all of the well established risk factors clearly implicate Es in the causation of BC (2)(3)(4)(5)(6). In this latter group, 17␤-estradiol (E 2 ) concentrations, all in the low picogram range, within narrow limits of serum and breast tissue levels (10)(11)(12)(13), are sufficient to increase sporadic BC risk. Therefore, it is essential to gain a better understanding of how Es, at these physiological concentrations, elicit their oncogenic effects in susceptible target tissues.…”