Binding of ovarian steroids to erythrocytes in patients with sickle cell disease; effects on cell sickling and osmotic fragility.
Ovarian steroids appear to influence the manifestations of sickle cell disease (SCD); oestrogens can adversely affect erythrocyte function, whereas progestogens may inhibit sickling and decrease the osmotic fragility of erythrocytes. The aims of the present studies were: (i) to characterise the binding of oestradiol and progesterone to erythrocytes from women with HbSS, HbSC and HbAA genotypes; (ii) to investigate whether steroids modulate susceptibility to sickling or osmotic fragility of HbSS and HbAA erythrocytes. Erythrocytes were incubated for 1h with [3H]-steroids at 4 and 37 degrees C. Binding of both oestradiol and progesterone was independent of temperature and steroid concentration, but was decreased by sequential "washing" of erythrocytes in fresh incubation buffer. Binding capacity was 80 +/- 6% greater for oestradiol (versus progesterone) in all three genotypes, and binding of both steroids was decreased by > or = 70% in HbSS erythrocytes compared to HbSC or HbAA erythrocytes. Pre-incubation of erythrocytes with 35 microM oestradiol or 30 microM progesterone had no significant effect on susceptibility of HbSS and HbAA erythrocytes to sickling, or on osmotic fragility. We conclude that both oestradiol and progesterone bind in a low affinity, non-saturable manner to erythrocytes with decreased binding in cells from women with HbSS. However, steroid binding does not affect susceptibility to sickling or osmotic fragility irrespective of haemoglobin genotype.
Yoong
Wai C
WC
University Department of Obstetrics and Gynaecology, North Middlesex Hospital, Sterling Way, London N18 1QX, UK. wyoong77@hotmail.com
Tuck
Susan M
SM
Michael
Anthony E
AE
D000328:Adult; D000755:Anemia, Sickle Cell / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006441:Hemoglobin A / Q000378:metabolism; D006450:Hemoglobin SC Disease / Q000378:metabolism; D006451:Hemoglobin, Sickle / Q000378:metabolism; D006454:Hemoglobins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009995:Osmosis; D010053:Ovary / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism*; D011485:Protein Binding; D013696:Temperature; D013997:Time Factors
D006451:Hemoglobin, Sickle; D006454:Hemoglobins; C028672:hemoglobin AA; D011374:Progesterone; D004958:Estradiol; D006441:Hemoglobin A