Effect Of Estrogen Priming Research Articles

Estradiol Priming Improves Gonadotrope Sensitivity and Pro-Inflammatory Cytokines in Obese Women.

Obesity is associated with a pro-inflammatory state and relative hypogonadotropic hypogonadism. Estrogen (E2) is a potential link between these phenomena because it exhibits negative feedback on gonadotropin secretion and also inhibits production of pro-inflammatory cytokines. We sought to examine the effect of estrogen priming on the hypothalamic-pituitary-ovarian axis in obesity. This was an interventional study at an academic center of 11 obese and 10 normal-weight (NW) women. A frequent blood-sampling study and one month of daily urinary collection were performed before and after administration of transdermal estradiol 0.1 mg/d for one entire menstrual cycle. Serum LH and FSH before and after GnRH stimulation, and urinary estrogen and progesterone metabolites were measured. E2 increased LH pulse amplitude and FSH response to GnRH (P = .048, and P < .03, respectively) in obese but not NW women. After E2 priming, ovulatory obese but not NW women had a 25% increase in luteal progesterone (P = .01). Obese women had significantly higher baseline IL-6, IL-10, TGF-β, and IL-12 compared with NW (all P < .05); these levels were reduced after E2 (-6% for IL-1β, -21% for IL-8, -5% for TGF-β, -5% for IL-12; all P < .05) in obese but not in NW women. E2 priming seems to improve hypothalamic-pituitary-ovarian axis function and systemic inflammation in ovulatory, obese women. Reducing chronic inflammation at the pituitary level may decrease the burden of obesity on fertility.

Preliminary genetic imaging study of the association between estrogen receptor-α gene polymorphisms and harsh human maternal parenting

A failure of neural changes initiated by the estrogen surge in late pregnancy to reverse the valence of infant stimuli from aversive to rewarding is associated with dysfunctional maternal behavior in nonhuman mammals. Estrogen receptor-α plays the crucial role in mediating these neural effects of estrogen priming. This preliminary study examines associations between estrogen receptor-α gene polymorphisms and human maternal behavior. Two polymorphisms were associated with human negative maternal parenting. Furthermore, hemodynamic responses in functional magnetic resonance imaging to child stimuli in neural regions associated with social cognition fully mediated the association between genetic variation and negative parenting. This suggests testable hypotheses regarding a biological pathway between genetic variants and dysfunctional human maternal parenting.

Effect of estrogen priming through luteal phase and stimulation phase in poor responders in in-vitro fertilization

To verify whether a novel protocol administering E(2) during the luteal phase of the preceding cycle and during ovarian stimulation in GnRH antagonist cycle could enhance follicular response and hence improve outcomes in poor responders. In this retrospective analysis, a total of 155 poor responder patients subjected to IVF/ICSI were analyzed. All the patients had history of more than one prior IVF cycle failure with poor response (less than 5 oocytes retrieved and/or maximal E₂ level less than 500 pg/mL) by using conventional long agonist or antagonist protocol. In luteal E2 treatment protocol (n = 86), oral estradiol valerate 4 mg/day was initiated on luteal day 21 and either stopped at menstrual cycle day 3 (Protocol A, n = 28) or continued during the period of ovarian stimulation until the day of hCG injection (Protocol B, n = 58). IVF parameters and pregnancy outcome of luteal E2 treatments group were compared with a standard GnRH antagonist protocol (n = 69) which the patients received no hormonal pretreatment. Compared to standard GnRH antagonist protocol, cancellation rate was lower with luteal E2 group (15.1% vs 37.7%, p < 0.01). Moreover, patients treated with luteal estrogen resulted in an increased number of oocytes retrieved (4.5 ± 2.9 vs 3.2 ± 1.9; p < 0.01). A trend toward increase in number of normally fertilized embryos (2.9 ± 2.1vs 2.3 ± 1.9; p = 0.043), and increased prevalence of good quality embryos (51.2% vs 25%; p = 0.047) were noted. Comparing protocol A and B, there were no significant difference between embryologic data, however there were slight increase in ongoing pregnancy rate in protocol B compared to A (27.1% vs 20%, p = 0.357), although statistical significance was not achieved. Estrogen priming through luteal phase and stimulation phase improved ovarian responsiveness and this may lead to an increase in pregnancy rate in poor responders with failed cycle.

The effects of estrogen priming and puberty on the growth hormone response to standardized treadmill exercise.

The effects of estrogen priming and puberty on the growth hormone response to standardized treadmill exercise.

The effects of estrogen priming and puberty on the growth hormone response to standardized treadmill exercise and arginine-insulin in normal girls and boys.

To determine the effects of puberty and estrogen priming on the GH response to standardized treadmill exercise and arginine-insulin in normal boys and girls, we performed tests in 84 normal children (41 girls and 43 boys) representing all stages of puberty. A subset of the prepubertal children received the tests twice, with or without the administration of ethinyl estradiol (40 micrograms/m2 daily) for 2 days before the tests. The peak GH response to the three tests increased significantly with pubertal stage (r = 0.57; P < 0.0001), but did not differ between boys and girls at the same stage. With advancing puberty, the percentage of normal children who failed to attain a GH level greater than 7 micrograms/L during any of the three tests declined from 61% at pubertal stage 1 to 44% at stage 2, 11% at stage 3, and 0% at stages 4 and 5. Administration of estrogen to the prepubertal subjects raised the normal range for the peak GH response to the three tests from 1.9-20.3 to 7.2-40.5 micrograms/L. We conclude that both puberty and estrogen administration significantly increase the peak GH response to exercise, arginine, or insulin in normal subjects. Moreover, the conventional criterion that the peak GH response to three stimulation tests should exceed 7 micrograms/L was applicable in our study only to subjects who had attained pubertal stage 4 or 5 or who had received estrogen administration.

The effects of estrogen priming and puberty on the growth hormone response to standardized treadmill exercise and arginine-insulin in normal girls and boys

The effects of estrogen priming and puberty on the growth hormone response to standardized treadmill exercise and arginine-insulin in normal girls and boys

Early Follicle Growth in the Juvenile Macaca Monkey Ovary: The Effects of Estrogen Priming and Follicle-Stimulating Hormone1

The mechanism(s) that drives preantral and early antral follicle growth in the primate ovary is poorly understood. We previously reported that estrogen does not stimulate preantral or early antral follicle growth in juvenile primates. The purpose of the present study was to determine whether estrogen priming may play a role in enhancing FSH-stimulated follicle growth. Eight juvenile monkeys received implants on Day 1 of silastic capsules containing estradiol (or vehicle) to elevate circulating estradiol levels. Daily FSH injections were initiated on Day 4 and continued for up to 12 days. The left ovary was removed on Day 8 and served as a control. Ovulation was induced, and a luteal phase followed. On the first day of menses, the estradiol (vehicle) capsule-FSH protocol was repeated. The remaining ovary was removed on Day 8 of the second cycle. The number and size of all follicles in both ovaries were evaluated by light microscopy. Results indicate that estrogen priming in the first cycle did not enhance growth of preantral or antral follicles, but did result in fewer developing follicles > 1.0 mm in diameter, this was accompanied by an increase in early atretic antral follicles of similar size. In the second cycle, an even further reduction in number and size of developing antral follicles > 1.0 mm in diameter was observed. These data suggest that pretreatment with exogenous estrogen has an anti-follicular action on follicle growth in these primates.

Estrogen influences dolichyl phosphate distribution among glycolipid pools in mouse uteri

The steroid hormone 17 beta-estradiol dramatically induces uterine N-linked glycoprotein assembly [Dutt, A., Tang, J.-P., Welply, J. K., & Carson, D. D. (1986) Endocrinology (Baltimore) 118, 661-673]. To determine the role that dolichyl phosphate availability plays in this induction, we studied the effects of estrogen priming on the content of dolichyl phosphate and the distribution of dolichyl phosphate among various glycolipids in uteri. Dolichol-linked saccharides were metabolically labeled to equilibrium with either [3H]glucosamine or [3H]mannose and extracted from primary explants of uterine tissue. The amount of dolichol-linked saccharide was calculated from the specific radioactivity determined for the corresponding sugar nucleotides extracted from the tissues. The major dolichol-linked saccharides identified were mannosylphosphoryldolichol (MPD), oligosaccharylpyrophosphoryldolichol (OSL), and N,N'-diacetylchitobiosylpyrophosphoryldolichol (CBL). Estrogen increased the levels of MPD and OSL 4-fold; however, CBL levels did not change. After 3 days of treatment, the levels of these glycolipids were very similar to those in uteri from pregnant mice. Remarkably, MPD constituted 90-95% of dolichol-linked saccharides detected under all conditions. The tissue contents of total dolichyl phosphate and alkali-labile dolichyl phosphate, presumably MPD, were estimated by liquid chromatography. The levels of alkali-labile dolichyl phosphate determined in this way were in good agreement with the values estimated for MPD by metabolic labeling; moreover, alkali-labile dolichyl phosphate constituted 50-98% of the total dolichyl phosphate pool. The variations in MPD content depended upon the steroid hormone influence, most notably that of estrogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of body weight, adrenal status, and estrogen priming on hypothalamic progestin receptors in male and female rats

Some laboratories have reported sex differences in the effect of estrogen priming on neural progestin receptor concentration, whereas others find no such differences. The present studies sought to identify experimental variables which might differentially influence the measurable level of hypothalamic cytosol progestin receptors in adult male and female rats. The influence of three variables, body weight, adrenal status, and estrogen priming regimen, was evaluated. Treatment with low doses of estrogen (2 or 8 micrograms of estradiol benzoate (EB) 48 hr before sacrifice) was slightly but not significantly more effective in elevating hypothalamic progestin receptor content in age-matched females than in males despite the 40% greater body weights of males. When the same doses of EB were administered per 200 gm of body weight to animals with and without adrenal glands, both basal and estrogen-induced levels of hypothalamic progestin receptor were significantly higher in adrenalectomized/gonadectomized rats than in rats which were gonadectomized only, regardless of sex. There was no significant effect of sex or any interaction between sex, adrenal status, or estrogen priming dose. The only significant sex difference in brain progestin receptors occurred when weight-matched males and females received multiple injections of higher priming doses of estrogen (three daily injections of 10 micrograms of EB). Under these conditions, females showed up to 2-fold higher levels of hypothalamic progestin receptors than males, regardless of adrenal status. These data suggest that sex differences may exist in the neural progestin receptor systems of male and female rats, but the relationship of these differences to sex differences in neuroendocrine function or behavior is not clear.

In vitro luteinizing hormone-releasing hormone release from superfused rat hypothalami: site of action of progesterone and effect of estrogen priming.

The study examined the effect of estrogen priming on progesterone (P4)-induced LHRH release, the tissue site of action of P4, and the effect of 5 alpha-dihydroxyprogesterone (5 alpha-DHP) on LHRH release from hypothalamic fragments superfused in vitro. Immature female rats were ovariectomized (OVX) and, at 28 days of age, Silastic capsules containing estradiol (E2) were implanted. Two days later, animals were killed and hypothalamic fragments were removed and transferred to superfusion chambers. The hypothalamic units received P4 or 5 alpha-DHP delivered in an intermittent mode (10-min on, 20-min off). LHRH was determined in perfusates by RIA. After the input characteristics of different infusion modes (single pulses, intermittent, and continuous) of P4 infused into superfusion chambers were assessed, an intermittent infusion mode (10-min on, 20-min off) was selected for further examinations. In the mediobasal hypothalamic-anterior hypothalamic-preoptic area (MBH-AHA-POA) tissue preparations, we observed: 1) an infusion of 5 alpha-DHP was ineffective in stimulating LHRH release; 2) the release pattern of LHRH in response to three different P4 doses (10, 20, and 50 ng/ml) was similar in terms of percent changes (202% to 219% over control values); and 3) E2 priming was absolutely required for P4-stimulated LHRH release, and this requirement appeared to be dose dependent. Upon an examination of three hypothalamic tissue boundaries [the MBH, the POA-suprachiasmatic nuclei (POA-SCN), and the median eminence (ME)] to better delineate the in vitro site of action of P4 on LHRH release, it was demonstrated that the MBH responded upon P4 infusion, whereas the POA-SCN was unable to do so. The ME also responded upon P4 infusion, and LHRH release followed closely the pulsatile administration of P4 since upon each challenge of the steroid at the concentration of 10 or 20 ng/ml, a significant rise in LHRH release occurred. However, the temporal patterns of LHRH release from the ME appears to be different from those obtained from the MBH as well as the MBH-AHA-POA. These observations demonstrate that an intermittent infusion of P4, but not 5 alpha-DHP, is effective in activating the neural LHRH apparatus. Estrogen is an obligatory requirement for this P4-stimulated LHRH release, and the neural site of action of P4 resides within the MBH. However, this steroid also can act directly upon the ME nerve terminals to release LHRH.

Hyperprolactinemia induced by an estrogen-progesterone synergy: quantitative and temporal effects of estrogen priming in monkeys.

We evaluated the quantitative and temporal characteristics of the estrogen component of an estrogen-progesterone synergy, which can induce hyperprolactinemia in macaques. In Exp I, six groups of monkeys were treated for 2 weeks with various doses of estradiol benzoate (EB), which resulted in peripheral estradiol concentrations of 250-1500 pg/ml, followed by 2 weeks of combined estrogen and progesterone treatment. In each of the groups, regardless of the dosages of estradiol benzoate alone, PRL concentrations remained within normal limits (approximately 18 ng/ml). In contrast, during the subsequent period of combined EB and progesterone therapy, hyperprolactinemia developed. The resultant PRL concentrations were not dependent on the dose of EB administered. In Exp II, three groups of monkeys were treated with EB (25 micrograms/kg) alone for various intervals and subsequently with both EB and progesterone for 14 days. When initiation of progesterone therapy was preceded by a 9- or 6-day period of estrogen priming, PRL concentrations were significantly (P less than 0.05) elevated within 3-4 days; in contrast, when the EB and progesterone treatments were initiated simultaneously, 8 days elapsed before the PRL elevations were significant. In a third experiment, to determine whether decidualized endometrium accounted for the increased PRL levels following estrogen and progesterone treatment, a hysterectomized monkey was treated with EB followed by combined EB and progesterone treatment. The PRL response was not different from that of intact monkeys similarly treated. From these findings we conclude 1) that the estrogen-progesterone synergy promoting PRL secretion is not of endometrial origin; 2) that approximately 1 week of estrogen priming is required for progesterone to induce PRL secretion; 3) and that the mode of action of estrogen is not dose dependent, but, rather, is a threshold effect.

Cytoplasmic progesterone receptors in the hypothalamus-preoptic area of the mouse: Effect of estrogen priming

A synthetic progestin, R5020, was used to identify cytoplasmic progestin receptors in the hypothalamuspreoptic area (HPOA) of ovariectomized mice. These high-affinity receptors exhibited an apparent dissociation constant of approx. 1 nM. The receptors were specific for progestins. [ 3H]R5020 binding was inhibited by more than 50% with a 50-fold excess of either radioinert R5020 or progesterone. 5α-Dihydroprogesterone inhibited binding to a lesser extent. 3α-Hydroxy-5α-pregnane 20-one and cortisol did not compete for [ 3H]R5020 binding. Administration of estradiol benzoate (10 μg), 48 h prior to death, resulted in a 54% increase in the HPOA progestin receptor concentration when compared to oil-injected controls. These data demonstrate that there are specific and saturable cytoplasmic progestin receptors in the mouse HPOA and that the concentration of these receptors is increased after estrogen treatment.

The effect of estrogen priming of hypogonadal women on the release of gonadotropins and prolactin in response to 2-hydroxyestradiol

We have previously shown that the administration of a 2-hydroxyestradiol (20H-E 2) infusion 9250 μg/h x 4 h) to hypogonadal women resulted in a selective increase in the levels of circulating prolactin (PRL) without changes in LH or FSH. The present study concerns the effect of estrogen priming of hypogonadal women on the release of gonadotropins and PRL in response to an identical 20H-E 2 infusion. Estrogen priming consisted of a 5 day course of orally administered ethinyl estradiol at a daily dose of 300 μg. Significant (P < 0.05) inhibition of LH release was observed within 1 h of the onset of the 20H-E 2 infusion reaching a nadir (−25 ± 2%) by 3.75 h. The circulating levels of FSH remained unaltered for the duration of the 8 h study. In contrast, significant (P < 0.05) increments in the release of PRL could clearly be detected after a lag period of 1.5 h reaching a peak (+91 ± 11%) by 4 h. These and previous findings demonstrate that the inhibitory influence of 20H-E 2 on gonadotropin secretion is conditional upon prior estrogen priming while the ability of 20H-E 2 to stimulate the release of PRL is not.

The effect of estrogen priming on induction of labor with prostaglandins

A double-blind, randomized study was designed to determine whether estrogen “priming” of the unripe cervix followed by prostaglandin induction of labor would have a synergistic effect on cervical ripening and improve the success rate of induction. One hundred near-term patients with Bishop scores ≤4 received an intramuscular injection of either 10 mg of estradiol valerate or a placebo 48 hours prior to induction of labor with oral prostaglandin E2. The serial changes in Bishop scores were very similar in both groups. The success rate of induction in the study group (69.8%) was not statistically different from that in the control group (61.9%). The duration of labor was 9.9 ± 4.1 hours in the study group versus 9.1 ± 3.7 hours in the control group (not significant). This study showed that 10 mg of estradiol valerate had no detectable effect on the unripe cervix near term and did not show a synergistic effect with prostaglandins during induction of labor.

Effects of Actinomycin D and Estrogen Priming on Decidual Growth in Ovariectomized Mice

Ovariectomized mice were primed for 2 days with estradiol and/or actinomycin D. In order to evaluate the effects of these treatments on endometrial cell proliferation, colchicine and [3H]-thymidine were administered shortly before killing groups of animals at days 4 and 5 after priming (the latter groups received 500 micrograms progesterone plus 10 ng estradiol 24 h before killing). The same priming treatments were administered 3 days before starting hormonal treatment eliciting uterine sensitivity to decidualization (incuded by intrauterine oil injection). The comparison of labeling and mitotic indices and of decidual tissue weights between experimental groups showed that under such conditions: (1) actinomycin D only partly inhibits the effects of estrogen priming: the increase in cell division obtained on day 4 after priming remains unchanged in all three endometrial components while the increase in stromal mitotic activity at day 5 and further decidual growth are reduced, (2) since the inhibition rate of these parameters is greater in non-primed than in primed animals, it appears that estrogen priming counteracts the antagonistic action of actinomycin D.

The mechanism of the action of progesterone--the effects of estrogen priming on the nucleus (author's transl)

Estrogen priming is necessary for progesterone action, and it was demonstrated that the priming increases progesterone-receptor in the cytoplasm of the rabbit uterus. However, it is not yet known whether estrogen priming results in some changes of the nuclear constituent for progesterone action or not, while progesterone-receptor complex enters into the nucleus and binds to the chromatin acceptor site. The estrogen priming effect on the nucleus for the mechanism of action of progesterone is the subject of this paper.The 274,200 x g supernatant of rabbit uterine homogenate was used as cytosol. The nuclei and chromatins were prepared by the method in Table 1. The cytosol labeled with 3H-progesterone was incubated with nuclei obtained from estrogen primed or castrated rabbit and then nuclear radioactivity was counted. Estrogen priming increased the nonspecific binding sites of progesterone-cytosol complex but did not increase the specific binding sites in the nuclei as in Fig. 2.Uterine cytosol of castrated rabbit gives progesterone-5S binding and that of estrogen primed rabbit gives progesterone-8S and 5S bindings as in Fig. 1. 3H-progesterone-8S was fractionated as in Fig.1, and it was then incubated with the uterine chromatins obtained from the castrated or primed rabbits. Radioactivities of these chromatins were counted. Progesterone-8S complexes bound to both estrogen primed and estrogen non-primed chromatins in almost equal amount per DNA as in Fig. 3. It is indicated that the chromatin acceptor sites (per DNA) for progesterone-receptor complex is equal in spite of estrogen priming. The activity of RNA synthesis by progesterone-8S on the uterine chromatins of primed and non-primed rabbits was almost same in amount per DNA as in Fig. 4.These results indicate that the function of estrogen priming on the mechanism of action of progesterone is the synthesis of progesterone-receptor and the increase of nonspecific binding sites of progesterone·macromolecule (non-specific binding protein) in the nucleus.

Effect of oestrogen priming on the pattern of progesterone metabolism in the mouse uterus.

The effect of estrogen priming on the pattern of progesterone metabolism was investigated in mouse uterus. 5 or 500 pg of tritiated progesterone was injected intraluminally into both uterine horns of spayed mice 1 or 6 days after estrogen priming. Uteri were removed 5 minutes postinjection and immediately extracted and separated by thin-layer chromatography. Metabolism of progesterone was greatest immediately after estrogen priming (p less than .001) at which time C20-ketone metabolites predominated over ring A metabolites. However 6 days after priming ring A metabolism predominated over C20-ketone metabolism (p less than .01). The difference in progesterone dosage had no marked effect on these ratios. It is concluded that the estrogen effect was not influenced by the dose of progesterone (p less than .05).

Induction of estrus in female mice: Estrogen-progesterone interactions

Accumulating evidence indicates that progesterone can have biphasic, facilitatory and inhibitory, effects on sexual receptivity in the guinea pig and rat. The present study sought to extend the generality of this work to the female mouse. The data indicated that 24 hr following the facilitation of the induction of sexual receptivity in estrogen-primed females by an injection of progesterone, a second injection of progesterone was relatively ineffective in inducing a second period of receptivity. The magnitude of this inhibitory effect appeared to be a function of dose of estrogen priming, with the greatest inhibition occurring in groups primed with relatively low doses of estrogen. The postreceptivity refractoriness was not due to a reduction in the effect of estrogen priming, nor could it be attributed to the effects of repeated testing. Thus, progesterone can apparently exert biphasic effects on the induction of receptivity in female mice. In this regard, the mouse appears similar to the guinea pig and rat.

A biphasic influence of progesterone on sexual receptivity of spayed female rats

Recent studies on sexual receptivity have suggested that there are striking differences in response to progesterone between ovariectomized, estrogen-primed rats and guinea pigs. Only in guinea pigs was a post-receptivity refractory period observed 24 hr after progesterone treatment. The current study sought to determine if the response to progesterone was influenced by the amount of priming estrogen used. Spayed female rats were primed with threshold amounts of estrogen for inducing receptivity and then subjected to different hormone and testing procedures. Progesterone facilitated receptivity shortly after the initial administration and induced a non-receptive condition 24 hr later. The post-receptivity refractoriness was not due to the effect of testing or to a passive reduction in the effect of estrogen priming and was prevented by additional estrogen. Under the conditions used in the present study progesterone exerts a biphasic influence on sexual receptivity of rats similar to that previously demonstrated for guinea pigs.