The ovarian steroid progesterone affects reproductive physiology by regulating the expression of specific genes in target tissues. In an attempt to address the question of whether the ovary itself is a target tissue for progesterone action, we have examined the localization and regulation of progesterone receptor (PR) mRNA in the rat ovary. We used the polymerase chain reaction to clone the steroid-binding domain of the rat PR from uterine cDNA and used this as a probe to isolate a larger cDNA from a rat placental cDNA library. We used RNA filter hybridization, a quantitative reverse transcription-polymerase chain reaction amplification assay, and in situ hybridization to detect PR mRNA in the rat ovary. Expression of the PR gene was initially studied in an immature animal model; 23-day-old rats were treated with either PMSG or PMSG followed by hCG. We found little or no PR mRNA in the ovaries of control or PMSG-treated animals; however, the mRNA was highly expressed in the granuiosa cells of large follic...

Transient Expression of Progesterone Receptor Messenger RNA in Ovarian Granuiosa Cells after the Preovulatory Luteinizing Hormone Surge

Hox genes have a well-characterized role in embryonic development, where they determine identity along the anteroposterior body axis. Hox genes are expressed not only during embryogenesis but also in the adult, where they are necessary for functional differentiation. Despite the known function of these genes as transcription factors, few regulatory mechanisms that drive Hox expression are known. Recently, several hormones and their cognate receptors have been shown to regulate Hox gene expression and thereby mediate development in the embryo as well as functional differentiation in the adult organism. Estradiol, progesterone, testosterone, retinoic acid, and vitamin D have been shown to regulate Hox gene expression. In the embryo, the endocrine system directs axial Hox gene expression; aberrant Hox gene expression due to exposure to endocrine disruptors contributes to the teratogenicity of these compounds. In the adult, endocrine regulation of Hox genes is necessary to enable such diverse functions as hematopoiesis and reproduction; endocrinopathies can result in dysregulated HOX gene expression affecting physiology. By regulating HOX genes, hormonal signals utilize a conserved mechanism that allows generation of structural and functional diversity in both developing and adult tissues. This review discusses endocrine Hox regulation and its impact on physiology and human pathology.

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Endocrine regulation of HOX genes.

Implantation is an intricately timed event necessary in the process of viviparous birth that allows mammals to nourish and protect their young during early development. Human implantation begins when the blastocyst both assumes a fixed position in the uterus and establishes a more intimate relationship with the endometrium. Due to the impracticalities of studying implantation in humans, animal models are necessary to decipher the molecular and mechanical events of this process. This review will discuss the differences in implantation between different animal models and describe how these differences can be utilized to investigate discrete implantation stages. In addition, factors that have been shown to be involved in implantation in the human and other various animal models including growth factors, cytokines, modulators of cell adhesion, and developmental factors will be discussed, and examples from each will be given.

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Animal models of implantation.

DL-Centchroman (67/20; INN: Ormeloxifene) synthesized at the Central Drug Research Institute, Lucknow, is a nonsteroidal once-a-week oral contraceptive. It was introduced in Delhi in July, 1991, marketed in India in 1992 as Saheli and Choice-7 (Hindustan Latex Ltd., Thiruvananthapuram) and Centron (Torrent Pharmaceuticals India Ltd., Ahmedabad), and included in the National Family Welfare Programme in 1995.5 According to post-marketing surveillance, approximately 100,000 women were using this pill and approximately 1100,000 menstrual cycles were covered until 1996. It is a unique need-oriented contraceptive being effective when taken immediately after coitus or routinely as a weekly pill and has the advantage of less frequent administration. Its contraceptive action is quickly reversible. It has long terminal serum halflife of 168 hr in women and exhibits duration of anti-implantation/estrogen antagonistic action of 120 hr, despite a short (24.1 hr) serum halflife, in the rat. In lactating women, it is excreted in milk in quantities considered unlikely to cause any deleterious effect on suckling babies. In phase II and III multicentric trials as a contraceptive, children born of method-and-user failure pregnancies showed normal milestones, without any congenital anomaly. Reports of its promising action in the management of certain hormone-related clinical disorders are available. It has an excellent therapeutic index and is considered safe for chronic administration.

Centchroman, a selective estrogen receptor modulator, as a contraceptive and for the management of hormone-related clinical disorders.

https://www.fertstert.org/article/S0015-0282(11)02193-5/pdf

It’s time to pay attention to the endometrium

Intrinsic role of preovulatory and nidatory estrogen and progesterone and presence of viable blastocysts in utero in pinopod development on the uterine luminal epithelial surface and correlation between time of their development and onset of endometrial sensitivity were investigated In adult rats, pinopods were observed on the entire epithelium even before secretion of nidatory estrogen, ie at 1400 h on day 4 post-coitum (pc) Apparently, their number increased, more so on the antimesometrial than the mesometrial side, at 1000 h on day 5, but were fewer and mostly collapsed at 1000 h on day 6 Pinopods on day 4 were located within epithelial depressions and foldings, but protruded from the surface on days 5 and 6 Normal pinopods were also present on day 8 pc in rats under delayed implantation, but an implantation-inducing dose of estradiol-17 beta administered about 18 h earlier caused their collapse like that on day 6 in intact rats Development and appearance of pinopods in intact or delayed rats was unaffected when native preimplantation embryos were prevented from entering the uterus Normal pinopods were seen in immature rats receiving progesterone for at least 3 days or cyproterone acetate for 4 days, but not after estradiol alone In animals receiving progesterone or priming/sensitizing estradiol in addition to progesterone, the decidual response was suboptimal, irrespective of the presence of pinopods on the day of stimulation In animals in which a condition mimicking preimplantation had been produced by suitable hormone supplementation, optimal endometrial sensitivity and decidual response were elicited, even though most pinopods appeared collapsed, resembling those on day 6 in intact rats and about 18 h after estradiol in implantation-delayed rats Findings confirm that pinopod development on uterine luminal epithelium was dependent on progesterone alone and demonstrate that: (i) preovulatory (priming) or nidatory (endometrial sensitizing) estrogen or viable blastocysts in utero have no role in their development Nidatory estrogen, instead, appears to limit pinopod development by causing their collapse; (ii) pinopod development/presence on the endometrial surface might indicate the uterus coming into a period of sensitivity rather than actually being in it and might thus serve as a useful marker of "transfer window" rather than "implantation window"; (iii) in the rat, pinopod development might serve as an alternate assay for evaluation of progestational activity of newer test agents

Correlation of pinopod development on uterine luminal epithelial surface with hormonal events and endometrial sensitivity in rat

RU-38486 or ZK-98734 treatment (3 mg/day, s.c.) to intact or hysterectomized adult female rats on Days 5-7 post coitum induced changes characteristic of luteolysis. Ultrastructurally, the luteal cells exhibited an extensive vacuolization of the cytoplasm and perinuclear areas, degeneration of mitochondrial cristae, massive accumulation of lipid droplets, increase in number of lysosome like granules and heterochromatinization of the nucleus. In general, RU-38486 induced more marked degeneration of the luteal cells than did ZK-98734. There was also a significant decrease in peripheral plasma progesterone concentrations in treated rats. We suggest that these antiprogestagens act via inhibition of luteal function in addition to their antagonism at the uterine progesterone receptor level.

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Luteolytic action of two antiprogestational agents (RU-38486 and ZK-98734) in the rat.

Inhibition of progesterone-induced development of giant mitochondria in uterine glandular epithelial cells by an antiestrogen in rat

Uterine estradiol and progesterone receptor concentration in relation to circulating hormone levels and histoarchitecture during high endometrial sensitivity and induced decidualization in guinea pigs

S. C. Maitra

Papers

Correlation of pinopod development on uterine luminal epithelial surface with hormonal events and endometrial sensitivity in rat

Luteolytic action of two antiprogestational agents (RU-38486 and ZK-98734) in the rat.

Inhibition of progesterone-induced development of giant mitochondria in uterine glandular epithelial cells by an antiestrogen in rat

Uterine estradiol and progesterone receptor concentration in relation to circulating hormone levels and histoarchitecture during high endometrial sensitivity and induced decidualization in guinea pigs