Progesterone, estradiol and their respective receptors in leiomyoma and adjacent normal myometria of black Kenyan women

Abstract

Scientific work has generated a concensus on the involvement of sex steroid hormones and their respective receptors in the development of uterine fibroids, but there are$ controversies as r to the levels of these hormones and receptors in this disease. The present effort was directed towards resolving this controversy and to provide information regarding the disease in the black (negroid) population in Kenya. Specimens of uterine leiomyomata and the adjacent normal myometria were collected from twenty patients undergoing hysterectomy, at the Kenyatta National Hospital Nairobi, for histological examination and analysis of progesterone (P4)' estradiol (E2), estrogen receptor (ER) and progesterone receptor (PR) levels. The tissues for hormonal and receptor measurements were homogenized and centrifuged at 27,000 x g for 40 minutes to yield a supernatant (cytosol). The cytosolic fluids were assayed for total protein as well as their binding activity to estradiol and progesterone tracers. Fractions of cytosol were incubated separately with [(2,4,7-3H)Estradiol] and [17a-Hydroxyl(l,3,6,7- 3H)]Progesterone at 4°c for 48 hours. Using centrifugation bound and unbound ligand were then separated by charcoal absorption. The supernatant was counted in a Beta Liquid Scintillation Counter. The amount of bound hormone per mg protein was calculated. Estrogen and progesterone receptors (ER & PR) were indirectly determined by calculating the amount of bound hormone per mg cytosolic protein while the estradiol and progesterone levels were determined by radioimmunoassay (RIA). The results showed that the adjacent normal myometria contained significantly higher levels of E2 (181.1 % : P<0.001) and P4 (240.6% : P<0.001) compared to the leiomyomata. The total· P4 in the uterine tissues i.e fibroid and myometrium was higher (628.4 %) than total E2 in the same tissues. On the contrary, the uterine leiomyomata contained higher levels of ER (147.6 % P<0.001) and PR (178.7 % : P<0.001) compared to the myometria. The total ER was higher (180.5 %) than total PRo It was therefore concluded that women in the black population In Kenya have higher levels of E2 and P4 in the adjacent normal myometrium compared to the leiomyoma. On the other hand, ER and PR concentrations were higher in the leiomyoma compared to the adjacent normal myometrium. In the same population total ER concentration i.e ER in both fibroid and myometrium were higher than total PR in the same tissues, whereas, total P4 levels were higher than E2. It is postulated that relative proportions of E2, P4, ER and PR in individual patients uterine tissue may be important In the pathogenesis of fibroids in the black population in Kenya. It is further suggested that treatment and management of the problem should involve manipulations of the sex steroids and their receptors. However, research should continue in order to indentify a nonsurgical means of treating the disease. This would be an important public health initiative especially in the black population where the incidence of fibroids is higher, surgical complications commoner and childbearing the center of matrimonial harmony. While hoping for such a breakthrough the importance of early diagnosis and the detection of high risk groups should be emphasized in the clinical management of this disease since the current drug treatment modality only reduces uterine size.