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  • Title: Expression of progesterone receptor mRNA in the endometrium during the normal menstrual cycle and in Norplant users.
    Author: Lau TM, Witjaksono J, Affandi B, Rogers PA.
    Journal: Hum Reprod; 1996 Dec; 11(12):2629-34. PubMed ID: 9021364.
    Abstract:
    The expression of endometrial progesterone receptor mRNA during the human menstrual cycle and in Norplant users was studied using digoxigenin-labelled ribonucleic probes for in-situ hybridization on 6 microns paraffin embedded endometrial sections. The staining intensity was scored blind semi-quantitatively. Blood ovarian steroid concentrations were measured in Norplant users. All data were analysed by analysis of variance. Glandular progesterone receptor mRNA concentrations were low during the menstrual-to-early proliferative stage but increased during the early-to-mid to late-proliferative stage then declined non-significantly over the secretory stage. No such variation was observed in stromal cells. Progesterone receptor mRNA concentrations were lower in Norplant than controls during early-to-mid to late-proliferative stages (in glandular epithelium and stroma) and during secretory stage (in stroma only). Norplant subjects with amenorrhoea had higher concentrations of stromal progesterone receptor mRNA but lower plasma oestrogen concentrations than subjects with breakthrough bleeding. The pattern of variation in progesterone receptor mRNA concentrations during the normal menstrual cycle resembles the published pattern for the receptor protein. The results demonstrate: (i) a differential sensitivity of glandular and stromal progesterone receptors to steroid regulation; (ii) in contrast to previous findings of an increase in immunoreactive progesterone receptor protein in Norplant endometrium, progesterone receptor mRNA concentrations in these tissues were reduced; and (iii) there was significantly more progesterone receptor mRNA in subjects with amenorrhoea than in those with breakthrough bleeding. At Monash Medical Center in Victoria, Australia, and at the University of Indonesia in Jakarta, researchers used digoxigenin-labeled ribonucleic probes for in-situ hybridization in the endometrium of 53 women across the normal menstrual cycle (controls) and of 39 Norplant users (cases), respectively, to examine the expression of progesterone receptor mRNA in the endometrium during the normal menstrual cycle and in Norplant users. They detected progesterone receptor mRNA in the glandular epithelium and stromal cells at all stages of the menstrual cycle. Concentrations of progesterone receptor mRNA staining in the glands increased from stage 1 (the menstrual to early proliferative stage), when there was little progesterone receptor mRNA staining, to stage 2 (early-to-mid proliferative to late proliferative stage) (1.35 vs. 2.25 staining intensity score; p 0.01). Thereafter, they fell steadily, but not significantly so. On the other hand, concentrations of progesterone receptor mRNA staining in the stroma did not vary during the menstrual cycle. Most endometria of Norplant users had detectable progesterone receptor mRNA in both the glandular epithelia and stromal cells. The endometria of Norplant users had less progesterone receptor mRNA staining in glandular epithelia than stage 2 of the cycle of the controls (1.5 vs. 2.25 score; p 0.01). The Norplant stroma also had less progesterone receptor mRNA than stages 2 (1.75 vs. 2.5 score; p 0.05) and 3 (1.75 vs. 2.5 score; p 0.01). Among Norplant users, the amenorrhea group had more progesterone receptor mRNA staining in the stroma than the bleeding group (2.5 vs. 1.75 score; p 0.05). It had lower plasma concentrations of estrogen than the bleeding group (200.8 vs. 523.9 pmol/l; p 0.05). There were no differences in the plasma progesterone concentrations, however. These findings confirm that there is a significant relationship between reduced endogenous estrogen concentrations and reduced breakthrough bleeding in users of progestin-only contraceptives. They show that glandular and stromal progesterone receptors have different sensitivity to steroid regulation.
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