Use of Immunocytochemistry of Progesterone and Estrogen Receptors for Endometrial Dating

Abstract

Endometrial progesterone and estrogen receptors were studied by immunocytochemistry using monoclonal antibodies during the menstrual cycle in normal women. We initially compared immunocytochemical staining of progesterone and estradiol receptors on endometrial fragments obtained by either aspiration or endometrial biopsy and found that immunocytochemistry could be performed easily on tissue obtained in either way. The immunocytochemical studies showed that the concentration and distribution of receptors changed markedly during the normal menstrual cycle. These changes were distributed in three characteristic phases. During phase I, corresponding to the midfollicular period (days 7-8), a small proportion (25%) of stromal and glandular cells stained positively for the progesterone receptor, whereas estrogen receptor staining was more intense and more frequent (50% of cells). Phase II, which included both the late follicular and early luteal periods (days 9-19), was characterized by a marked staining of progesterone receptors in the majority of glandular cells (75%) and somewhat less abundant and less frequent staining in stromal cells (50%). Estrogen receptor staining was present in about half of the glandular and stromal cells. Phase III, the mid- and late luteal period (days 21-27), was characterized by the disappearance of estrogen and progesterone receptor staining in glandular cells, although faint staining for both receptors was found in stromal cells. These variations in progesterone receptor staining are potentially useful for determining the effect of progesterone on endometrial maturation.

A dynamic shift of VEGF isoforms with a transient and selective progesterone-induced expression of VEGF189regulates angiogenesis and vascular permeability in human uterus

“…During their differentiation from mid-secretory phase to the end of pregnancy, predecidual cells sequentially express and secrete relaxin, prolactin, and IGFBP-1 (33), change their morphology in association with the appearance of smooth muscle ␣-actin (ref. 28 and this study), and express progesterone and estrogen (ER␤) receptors (27,34). The presence of type IV collagen, heparan sulfate proteoglycans (HSPG), and TIMP-3 during the mid-late secretory phase (days 24-26) (unpublished observations) reflects the production and assembly of a distinct pericellular basement membrane by differentiated decidual cells (35)(36)(37).…”

“…The steady-state expression of VEGF transcripts was increased by E 2 within 1-3 h and persisted for 12 days, whereas P for 1-24 h did not modify VEGF mRNA levels. To further analyze the role of P on VEGF expression, subconfluent cultures of endometrial stromal cells were treated for 14 days with E 2 ϩ P; these cells express estradiol and progesterone receptors (7,34).…”

“…5 B and C). Addition of aprotinin or an anti-uPA antibody with native V 189 did not significantly change the CP Immunocytochemical staining for VEGF or type IV collagen was evaluated semiquantitatively on endometrial sections, as described (24,34).…”

New Insight into Progesterone-dependent Signalization

“…In humans, the level of expression of both isoforms is different in the course of the menstrual cycle and in various types of cells. In the endometrium, their expression undergoes specific fluctuations: it increases during the follicular phase and decreases after the ovulation [22,23]. Estrogens induce mRNA and protein expression of both nPRs, especially of nPRB in chick oviduct, rat uterus and human endometrial cells.…”

“…This activity increases the B/A ratio in favor of isoform B. In turn, nPR isoforms are down-regulated in the presence of their specific ligand -P4 [22,23]. Diverse distribution of nPR isoforms in humans could implicate crucial clinical consequences.…”