Feedback Effects Of Estradiol Research Articles

Feedback effects of estradiol and progesterone on ovulation and fertility of dairy cows after gonadotropin-releasing hormone-induced release of luteinizing hormone

An experiment was conducted with the objective to determine the effects of estradiol, progesterone, presence of a corpus luteum (CL), and size of a dominant follicle on the characteristics and patterns of GnRH-induced LH release and subsequent ovulation during a timed artificial insemination (TAI) program, or a combination of these. In 70 lactating dairy cows, a total of 163 blood collection periods resulting in a GnRH-induced LH release were analyzed. Concentrations of LH were measured in hourly samples (0 through 6 h after GnRH) during each of the blood collection periods, whereas concentrations of progesterone and estradiol were measured in the sample before GnRH treatment (0 h). Measures of LH included time to LH peak concentration during the 6-h blood collection period, the 2 largest concentrations of LH, mean, and variance of the 6 LH concentrations under each LH curve. Individual and combination effects of CL presence and a dominant follicle≤or >13.5mm, in addition to individual and combination effects of progesterone: low (<0.45 ng/mL; n=83), medium (0.53 to 2.41 ng/mL; n=25), and high (2.66 to 10.7 ng/mL; n=55), and estradiol: low (<4.0 pg/mL; n=89) and high (≥4.0 pg/mL; n=74) were independent variables in models to determine their influence on characteristics of LH and ovulation. Injections of GnRH induced LH release during 6 h after each of 163 injections. Measures of GnRH-induced LH concentration were inhibited at greater concentrations of progesterone and in the presence of a CL. In contrast, GnRH-induced LH concentrations were increased when estradiol was ≥4.0 pg/mL, but relatively unaffected by the size of the dominant follicle. Furthermore, resulting incidences of ovulation were decreased at greater progesterone concentrations and presence of a CL, and increased at greater estradiol concentrations and presence of follicles >13.5mm. In cows with or without a CL, the presence of a follicle >13.5mm did not increase mean LH concentration or incidence of ovulation. We conclude that when progesterone concentration exceeded 0.5 ng/mL at the time of GnRH treatment, subsequent LH concentrations and ovulation were suppressed. At that same concentration of progesterone or when concentrations of estradiol were ≥4 pg/mL, TAI pregnancy outcomes were improved in the face of similar incidences of ovulation suggesting greater progesterone or lesser estradiol at the time of AI may inhibit pregnancy establishment by other mechanisms.

Effects of estradiol or testosterone treatment on expression of gonadotropin subunit mRNAs and proteins in the pituitary of juvenile brown hagfish, Paramyxine atami

A single functional gonadotropin (GTH) comprising two subunits, α and β, was recently identified in the pituitary of brown hagfish (Paramyxine atami). Little is known about the feedback mechanisms that regulate these GTH subunits by sex steroids in the hagfish. The present study was designed to examine feedback effects of estradiol and testosterone on mRNA expression and protein expression of both GTHα and GTHβ subunits in the pituitary of the juvenile P. atami. Intraperitoneal administration of estradiol over the course of 27days resulted in substantial accumulation of immunoreactive (ir)-GTHα and ir-GTHβ in the adenohypophysis, but testosterone treatments over 27days had no effects on ir-GTHα or ir-GTHβ. Estradiol treatment for 1, 2, 4 or 14days had no effect on GTHα mRNA levels. In contrast, after 2days of estradiol treatment, GTHβ mRNA levels had increased significantly from baseline, while these levels were not affected after treatment over 1, 4, or 14days. After 14days of testosterone treatment, both GTHα and GTHβ mRNA levels had decreased significantly from baseline levels. These results indicate that estradiol acted primarily to suppress the secretion of GTH, and hence resulted in the accumulations of ir-GTHα and ir-GTHβ in the pituitary. On the other hand, testosterone appeared to suppress both the synthesis and the secretion of GTH. Thus, estradiol and testosterone probably differ in their effects on the regulation of pituitary GTH synthesis and secretion in juvenile hagfish.

227 EFFECTS OF A SINGLE DOSE OF A NONSTEROIDAL AROMATASE INHIBITOR ON OVARIAN FUNCTION IN CATTLE

Many countries have banned the use of estrogenic products in farm animals. Nonsteroidal aromatase inhibitors prevent the body from producing its own estrogen. The effects on the ovary are thought to be a result of suppression of estrogen-producing follicles and a rebound in endogenous levels of FSH through the removal of the negative feedback effect of estradiol. An experiment was designed to determine the effects of a nonsteroidal aromatase inhibitor, letrozole, on ovarian function in cattle. The specific objective was to test the hypothesis that letrozole will arrest growth of the dominant follicle, resulting in emergence of a new follicular wave at a predictable interval post-treatment. Beef heifers were assigned randomly to 4 groups and given phosphate-buffered saline [control; (n = 10)] or letrozole at a dose of 500 (n = 9), 250 (n = 10), or 125 (n = 10) μgkg-1 i.v. 4 days after follicular ablation (≈ 2.5 days after wave emergence, at the time dominant follicle selection is manifest). Blood samples were collected and ovarian structures were monitored daily by transrectal ultrasonography. Analysis of variance for repeated measures, one-way ANOVA, paired t-test, and 2-sample t-test were applied to the analysis of the data. The diameter profile of the dominant follicle was larger in heifers treated with letrozole than in control heifers (P &lt; 0.05). The intervals from treatment to new wave emergence and from treatment to onset of regression of the extant dominant follicle were longer (P &lt; 0.05) in heifers treated with letrozole than in controls, although variances in the intervals were not different. A small but significant reduction in circulating estradiol concentration was observed, and plasma LH concentrations were higher (P &lt; 0.05) in letrozole-treated heifers than in controls. Lower plasma concentrations of FSH in letrozole-treated heifers than in controls (P &lt; 0.03) was interpreted as an indirect effect resulting from prolonged follicular dominance. In summary, a single dose of letrozole did not induce regression of the extant dominant follicle, nor did it directly affect FSH release. Conversely, letrozole extended the lifespan of the dominant follicle, in association with increased endogenous levels of LH, thereby delaying the next FSH surge and subsequent follicular wave emergence. Results suggest that letrozole has potential as a nonsteroidal method of controlling ovarian function in cattle but further studies are needed to clarify dosage and timing of treatment. Research supported by the Natural Sciences and Engineering Research Council of Canada and Bioniche Life Science Inc.

Involvement of Catecholaminergic Systems in the Zona incerta in the Steroidal Control of Gonadotrophin Release and Female Sexual Behaviour

Previous reports have shown that dopamine (DA) in the zona incerta (ZI) has a stimulatory effect on gonadotrophin release. We have now investigated the possibility that steroids exert their feedback effects on the release of luteinizing hormone (LH) via catecholamine systems in the ZI. Since the same steroid regimes also stimulate female sexual behaviour, the possibility that the ZI is also involved in the control of sexual activity was investigated. Lesions in the ZI increased proceptive and receptive behaviour in oestrogen-primed ovariectomised rats that exhibited a low level of lordosis in a pre-lesion test and had no effect in receptive animals. Turnover rates (TR) of DA, noradrenaline (NA) and adrenaline were measured in the ZI, preoptic area (POA), arcuate nucleus (ARC), median eminence (ME) and ventromedial nucleus in ovariectomised rats treated 54 h before with either oil, oestradiol benzoate (OB) at 5, 10 or 50 micrograms/rat, or 5 micrograms/rat OB followed by 0.5 mg/rat progesterone (P) 48 h later. The TR as measured from the decline in concentration after alpha-methyltyrosine and changes in DOPAC concentration were correlated with the effect of the steroids on plasma LH and lordotic activity. Confirming previous reports, NA turnover in the POA and ME was increased, and DA turnover in the ME was decreased by steroids when they enhanced LH release. DA turnover in the ARC and ME was reduced when lordosis behaviour increased. Treatment with OB plus P stimulated LH release and sexual receptivity and at the same time significantly increased DA and NA turnover in the ZI. There was no correlation between these parameters after OB alone. This report shows that the DA system in the ZI may mediate the stimulatory effect of P on LH release in OB-primed rats but is not involved in the feedback effects of oestradiol alone. NA activity in the ZI is increased after OB plus P and may therefore also be concerned with stimulating LH release. The ZI is involved in the control of sexual behaviour, as electrolytic lesions in this area enhance receptivity and proceptivity, but the catecholamine systems in the ZI do not appear to mediate this control.

Opioid involvement in LH release during the negative feedback effects of oestradiol and progesterone in dairy cows

To create a clearly defined and uniform feedback phase of oestradiol, 1 mg oestradiol benzoate (OE2) was injected i.m. either 15-43 days post partum in 7 cows (Expt 1), or 12 h after prostaglandin oestrus synchronization of 4 cyclic cows (Expt 2 and 3). An endogenous opioid peptide (EOP) antagonist (250 mg naloxone), an EOP agonist (300 mg morphine), or a combination of the two was given in Expt 1, 2 and 3 respectively as a single i.v. injection in cows 16-18 h after OE2, i.e. in the negative feedback phase and before the expected onset of an induced luteinizing hormone (LH) surge. Blood samples were collected every 15 min for 1 h before and 2 h after each treatment. In Expt 1, naloxone failed to increase LH release when given during the negative feedback phase, but caused excessive release in one cow in which the LH surge had just begun. In all cows in Expt 2, morphine suppressed LH release (P less than 0.05). In Expt 3, naloxone prevented the suppressive effects of morphine for the first hour after treatment; a transient rise in LH occurred in one cow in which treatment was given 1 h before the start of the LH surge. In Expt 4, 250 mg naloxone was injected i.v. into 4 cows that had a plasma progesterone concentration of 1.5-3.1 ng mL-1 in the luteal phase of the oestrous cycle: naloxone failed to increase LH concentrations. It is concluded that LH can be further suppressed by opiates given to cows during the negative feedback phase of oestradiol.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating concentrations of LH and FSH and pituitary responsiveness to GnRH in intact and ovariectomized suckled beef cows in two levels of body condition

ABSTRACTThe effect of body condition on hypothalamic and pituitary function in post-partum suckled beef cows was studied. Thirty-eight Blue-Grey cows were calved at a body condition score of either 2·35 (L) or 2·80 (H), fed to maintain live weight and body condition thereafter and ovariectomized at either 5 or 9 weeks post partum. The H cows had higher LH pulse frequencies before ovariectomy (0·36 v. 0·28 pulses per h; P &lt; 0·05) and 15 days after ovariectomy (0·86 v. 0·72 pulses per h; P &lt; 0·01), indicating a direct effect of body condition on GnRH release from the hypothalamus. Body condition had no effect on the ability of the pituitary to release LH in response to a physiological dose (2·5 u.g) of GnRH in entire or ovariectomized cows at 5 or 9 weeks post partum. The magnitude of the increase in circulating levels of LH following GnRH injection was greater at 9 weeks compared with 5 weeks post partum (2·23 v. 1·73 u.g/1; P &lt; 0·001) in entire cows, but there was no difference between 5 and 9 weeks in ovariectomized cows. Following ovariectomy there was a 2·5-fold increase in LH pulse frequency within 15 days and LH pulse frequency approached 1 pulse per h in all treatments groups. It is concluded that both the hypothalamus and the pituitary are capable of functioning normally by 5 weeks post partum in suckled beef cows, that the pulsatile release of GnRH from the hypothalamus is inhibited, possibly due to a very high sensitivity to oestradiol, and that the sensitivity of the pituitary to the negative feedback effect of oestradiol may decrease with time post partum.

Estradiol feedback inhibition of luteinizing hormone concentrations in the anestrous sow2

The suppressive effects of exogenous 17 beta-estradiol (E2) on LH concentrations in sows that remained anestrus following weaning and in those that returned to estrus were evaluated. Four anestrous and four cyclic sows were treated subcutaneously with silastic implants containing E2 at 13 d after ovariectomy (d 0). Three anestrous and six cyclic sows received silastic implants without E2. Blood was collected at 6-h intervals from d -1 to d 12 and at 15-min intervals for 8 h on d -1, 2, 7 and 12. Sows were treated with 1 microgram GnRH/kg BW at the completion of each 8-h frequent sampling period. Blood was collected at intervals of 10 to 30 min for 3 h after GnRH treatment. Concentrations of E2 remained less than 5 pg/ml in sham-treated sows and were between 20 and 25 pg/ml in E2-treated females. Pulsatile LH concentrations was similar between anestrous and cyclic sows prior to implant treatment. Sham-treated anestrous sows had greater (P less than .05) pulse frequency and mean LH concentrations than E2-treated anestrous sows on d 2, 7 and 12. Differences in pulsatile LH concentrations between E2-treated and sham-treated cyclic sows were not detected. Pulse frequency was less (P less than .05) in E2-treated anestrous sows than in E2-treated cyclic sows on d 7 and 12. Peak LH concentrations were greater (P less than .05) in E2-treated cyclic sows than in E2-treated anestrous sows at each GnRH challenge. These results suggest that the hypothalamo-hypophyseal axis is more sensitive to the negative feedback effects of E2 in anestrous sows than in cyclic sows. In addition, chronic E2 treatment reduces pituitary responsiveness to GnRH to a greater extent in anestrous than in cyclic sows. Failure to return to estrus in swine may be due, at least in part, to an increased sensitivity of the hypothalamo-hypophyseal axis to the negative feedback effect of estradiol.

Basal and estradiol-induced release of gonadotropins in dairy cows with naturally occurring ovarian cysts

A study was conducted to identify relationships between serum sex steroid concentrations and release of gonadotropins in dairy cows with ovarian cysts. Cows with ovarian cysts were grouped according to sex steroid profiles as being under estrogenic (n = 6) or low steroid (n = 6) influence. All cows were submitted to a sampling and treatment protocol to 1) record basal pulsatile release of gonadotropins and 2) determine whether luteinizing hormone (LH) or follicle stimulating hormone (FSH) was released after sequential administration of exogenous estradiol and gonadotropin releasing hormone (GnRH) treatments were given 30 h apart. Basal LH was higher in the estrogen-influence group (P < 0.05). There were no differences between groups in basal FSH concentrations or frequency and amplitude of pulsatile LH or FSH release. Only one of the twelve cows, an individual from the low steroid group, had a preovulatory-like surge of gonadotropins after exogenous estradiol. All cows released LH and FSH in response to GnRH treatment, with no differences between groups. These results show that 1) there is considerable variation in pulsatile release of gonadotropins in cows with ovarian cysts, even among individuals with similar sex steroid profiles, and 2) suggest that a factor in the persistence, and perhaps initiation, of the cystic condition is refractoriness to the positive feedback effect of estradiol on gonadotropin release.

The Effect of Chronic and Acyclic Elevation of Circulating Androstenedione or Estrone Concentrations on Ovarian Function in the Rhesus Monkey

The concept that chronically elevated blood androstenedione concentrations increase the incidence of anovulation in the primate and that acyclic elevated basal blood androgen and/or estrogen concentrations cause abnormal gonadotropin secretion was studied. Regularly menstruating female rhesus monkeys were implanted sc with Silastic tubing filled with androstenedione or estrone and compared with controls. Androstenedione implants increased the serum androstenedione concentrations from 1.6 +/- 0.1 (SE) ng/ml to 6.30 +/- 0.27 ng/ml. By peripheral conversion the testosterone concentration increased from control values of 279 +/- 10 (SE) pg/ml to 1280 +/- 41 pg/ml. The testosterone concentration in the estrone-treated monkeys was 247 +/- 9.7 pg/ml. The estrone concentrations were: controls, 63.2 +/- 3.1 (SE) pg/ml; androstenedione-treated monkeys, 63.2 +/- 3.1 pg/ml; and estrone-treated animals, 150 +/- 5.3 pg/ml. The corresponding estradiol concentrations were: control animals, 35.1 +/- 2.1 (SE) pg/ml; androstenedione animals, 30.9 +/- 1.8 pg/ml; and estrone-treated monkeys, 65.7 +/- 3.9 pg/ml. There was no difference in the morning serum cortisol concentrations between any of the three groups or between ovulatory or anovulatory months. The chronic elevation of either androstenedione or estrone caused an increased incidence of anovulation compared with the controls. Increased estrogen concentrations caused increased anovulation during both summer and winter months; however, increased androgen concentrations caused increased anovulation only during the summer months. However, LH concentrations were unaffected in either group but were lower during anovulation months in all three groups. An LH or FSH surge followed an estradiol bolus in three of four control animals and four of six androstenedione-treated but none of the estrone-treated monkeys. Histological examination of ovarian biopsies demonstrated thickening of the tunica albuginea ovarii in androgen-treated ovaries and an apparent increased number of atretic follicles. Corpora lutea were absent in the ovaries of the estrogen-treated monkeys, but otherwise these ovaries were similar to those of controls. It is concluded that chronic acyclic elevation of blood androstenedione (and resultant testosterone) increases seasonal anovulation in the rhesus monkey. Increased blood estrone (and resultant estradiol) leads to almost complete anovulation throughout the year and renders the central nervous system-pituitary axis insensitive to positive feedback effect of estradiol. Neither treatment caused an increase in basal LH concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Relationship between pituitary nuclear oestrogen receptors and the release of LH, FSH and prolactin in the ewe.

Ovariectomized ewes were given a single injection (i.v.) of 100 micrograms oestradiol-17 beta. Nuclear oestrogen receptor values in the pituitary, as a function of total receptor concentrations, were 3.0 +/- 1.0% in controls, 56.0 +/- 5.4% at 1 h (P less than 0.001) and 6.5 +/- 2.1% at 6 h (P less than 0.05) after oestradiol injection. There was a fall in plasma LH values from 5.7 +/- 1.0 (preinjection) to 2.1 +/- 0.3 ng/ml (P less than 0.01) 4-6 h after oestradiol. At 13-21 h after injection plasma levels increased to 37 +/- 8 ng/ml (P less than 0.001). Plasma FSH levels declined from 840 +/- 18 to 506 +/- 48 ng/ml after 20-22 h (P less than 0.001). Plasma prolactin concentrations fell from 90 +/- 16 ng/ml before injection to 29 +/- 9 ng/ml at 1 h (P less than 0.05), and then rose to a maximum of nuclear compartmentalization of oestrogen receptors after a bolus injection of oestradiol was associated with the feedback effects of oestradiol on LH, FSH and prolactin release.

The influence of exogenous oestradiol benzoate on the pituitary responsiveness to LHRH during the puerperium in women.

The FSH and LH compared to 25 micrograms LHRH was measured in lactating women and the results compared to a similar group in whom lactation was suppressed by administration of bromocriptine shortly after delivery. The response was also measured in both groups after "challenge" with oestradiol benzoate. In lactating women the FSH response to LHRH was diminished following the oestradiol challenge, as compared with that in unchallenged women. At the same time the LH responses were low in both circumstances, indicating a negative feedback effect of oestradiol. However, the oestradiol challenge resulted in a significantly increased response of FSH and LH to LHRH in bromocriptine-treated puerperal women, i.e. a positive feedback effect of oestradiol. We concluded that this and previous experiments favour the hypothesis that the lactational amenorrhoea during hyperprolactinaemia is caused by hypothalamic changes due to a predominance of the negative feedback system.

Effect of estradiol benzoate and clomiphene on tyrosine hydroxylase activity and on luteinizing hormone and prolactin levels in ovariectomized rats

The effects of estradiol benzoate (EB) on tyrosine hydroxylase (TH) activity in the medial basal hypothalamus (MBH) and on plasma levels of luteinizing hormone (LH) and prolactin were studied in long-term ovariectomized rats. Administration of 10 μg EB produced significant elevation of TH activity on Days 1 and 3 following injection. LH levels were significantly lower than controls throughout the three day treatment period, although there was a significant increase from Day 1 to Day 2. TH activity and LH levels were inversely related throughout the experimental period. Clomiphene (15 μg/rat/day), a purported estrogen antagonist, was administered over a period of three days to control and EB-treated rats to determine whether the effect of EB on plasma LH levels was causally related to changes in TH activity. In rats receiving both EB and clomiphene, TH activity was lower and plasma LH was higher than after EB alone. The results support the hypothesis that the feedback effects of estradiol on LH release involve an action on the tuberoinfundibular dopaminergic (TIDA) neurons of the MBH and that clomiphene can oppose the inhibitory effect of estradiol on LH release by directly inhibiting TIDA neuron activity. Furthermore, EB-induced release of prolactin does not appear to involve detectable changes in the activity of TIDA neurons.

Effect of anaesthesia on the negative feedback action of gonadal steroids on gonadotrophin secretion in the ovariectomized guinea-pig.

The effects of urethane or sodium pentobarbitone anaesthesia on the feedback effects of oestradiol or progesterone on gonadotrophin secretion in the ovariectomized guinea-pig have been investigated. In the control experiments in which no steroids or vehicles were given the concentration of LH and FSH in samples of peripheral blood collected at intervals of 15 min varied in a random episodic manner. The mean level of LH was significantly greater in sodium pentobarbitone- and urethane-anaesthetized animals when compared with conscious animals, and in the conscious animals there was a progressive fall in mean LH level during the course of serial sampling. This effect was not observed in anaesthetized animals. Oestradiol benzoate (2 microgram s.c.) inhibited LH secretion in conscious animals and in those anaesthetized with sodium pentobarbitone, but not in urethane-anaesthetized guinea-pigs. Progesterone (200 microgram s.c.) progressively depressed plasma LH levels in conscious and urethane-anaesthetized animals, but not in guinea-pigs anaesthetized with sodium pentobarbitone. The effect of anaesthesia was the converse of that observed with oestradiol treatment. Significant changes in FSH secretion were not observed under any experimental conditions. These findings point to the existence of a mechanism in spayed guinea-pigs that restrains LH secretion, the action of which is reduced by anaesthesia and modified by oestradiol and progesterone.

Feedback effect of estradiol on follicle-stimulating hormone and prolactin secretion during the puerperium

Injections of 3 mg of estradiol benzoate were given to seven lactating women during the second and third weeks postpartum to study its effects on secretion of follicle-stimulating hormone (FSH) and prolactin during the subsequent 4 days. Administration of estradiol during the second week postpartum had no effect on serum levels of FSH and prolactin, however, 1 week later estradiol injection elicited a double effect: FSH levels decreased and prolactin concentrations increased. Early lactation seems to abolish the estrogen induced positive feedback effect on pituitary gonadotropin secretion. The negative effect of estrogen on FSH secretion and the positive effect on prolactin release became evident by the third week postpartum.

Failure of histamine to induce the release of luteinizing hormone in castrated rats primed with sex steroids.

Instituto de Investigaciones Cerebrales, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina (Received 10 March 1978) Injection of histamine into the third ventricle causes the release of luteinizing hormone (LH) in ovariectomized, steroid-primed and pro-oestrous rats (Donoso, Banzan &amp; Borzino, 1976; Donoso, 1978). In oestrous rabbits, intraventricular injection of large doses of histamine or injection of histamine into the mediobasal hypothalamus induces ovulation and secretion of progesterone by the ovaries (Sawyer, 1955; Endröczi &amp; Hilliard, 1965). However, histamine has no effect on the concentration of LH in the plasma of male rats (Donoso &amp; Banzan, 1976). Together, these results suggest that histamine is able to induce the release of LH both before ovulation and in the presence of an adequate hormonal background. The positive feedback effects of oestradiol and progesterone on the release of gonadotrophins are absent in male rats. Injection of oestradiol, progesterone or testosterone into steroid-primed