Thus, in addition to loss or attenuation of ligand-dependent ER activity, uterine hypoplasia in ERKO mice and endometrial hypoplasia in neonatal gilts treated with ICI 182,780 could reflect the uncoupling of ligand-independent ER signaling systems. These data also imply that the presence of a functional ER system may enhance the ability of target cells to respond to uterotropic growth factors. Therefore, development of ER-positive phenotype in specific cell populations of the uterine wall may not only dictate when and where estrogen can elicit classical, direct genomic effects on ER-positive target cells, but may also determine the extent to which locally produced uterotropic factors can influence uterine growth and endometrial maturation through estrogen-independent, membrane-initiated, ER-coupled pathways. Thus, for example, development of ER-positive character by GE cells in the neonatal porcine endometrium may increase their sensitivity to locally produced paracrine effectors of mitogenesis and/or cytodifferentiation such as insulin-like growth factor-I or epidermal growth factor. buy levaquin online
In summary, porcine uterine growth and endometrial histogenesis are developmentally regulated processes for which, at least grossly, ovarian support is not required until after PND 60. The porcine endometrium is ER negative at birth. Endometrial ER expression accompanies the appearance of new uterine glands, genesis of which occurs during the first few weeks of postnatal life. Development of ER in endometrial cells occurs progressively and in an ovary-independent manner between birth and PND 120. The dramatic onset of ER expression in nascent GE cells makes the ER a classic molecular marker of GE differentiation. Collectively, data reviewed here can be interpreted to suggest that development and activation of endometrial ER are required for endometrial adenogenesis and normal postnatal uterine growth in the pig. Recent reports indicating that both progesterone and retinyl palmitate can affect uterine protein synthesis, endometrial remodeling, and uterine growth in the neonatal pig suggest that, in addition to the ER, progesterone and retinoid receptor systems may be present and therefore involved in mechanisms regulating porcine endometrial maturation and uterine growth during the early postnatal period. Studies to confirm such suggestions, and to determine whether the recently identified ER is present, as in the rat uterus, or is involved in porcine endometrial development, remain to be conducted.