Negative effect of estradiol on luteinizing hormone throughout the ovulatory luteinizing hormone surge in mares

The negative effect of estradiol-17beta (E2) on LH, based on exogenous E2 treatments, and the reciprocal effect of LH on endogenous E2, based on hCG treatments, were studied throughout the ovulatory follicular wave during a total of 103 equine estrous cycles in seven experiments. An initial study developed E2 treatment protocols that approximated physiologic E2 concentrations during the estrous cycle. On Day 13 (ovulation = Day 0), when basal concentrations of E2 and LH precede the ovulatory surges, exogenous E2 significantly depressed LH concentrations to below basal levels. Ablation of all follicles > or = 10 mm when the largest was > or =20 mm resulted in an increase in percentage change in LH concentration within 8 h that was greater (P < 0.03) than for controls or E2-treated/follicle-ablated mares. Significant decreases in LH occurred when E2 was given when the largest follicle was either > or =25 mm, > or =28 mm, > or =35 mm, or near ovulation. Treatment with 200 or 2000 IU of hCG did not affect E2 concentrations during the initial portion of the LH surge (largest follicle, > or =25 mm), but 2000 IU significantly depressed E2 concentrations before ovulation (largest follicle, > or =35 mm). Results indicated a continuous negative effect of E2 on LH throughout the ovulatory follicular wave and may be related to the long LH surge and the long follicular phase in mares. Results also indicated that a reciprocal negative effect of LH on E2 does not develop until the E2 surge reaches a peak.     

Age-related alterations in pulsatile luteinizing hormone release: effects of long-term ovariectomy, repeated pregnancies and naloxone

Aging of the female reproductive system may be regulated by changes at the hypothalamic, pituitary, and ovarian levels. Long-term ovariectomy (LT-OVX) and/or multiple pregnancies delay age-related deterioration of several parameters of reproductive potential in rodents. We tested whether long-term suppression of cyclic ovarian hormone release that is normally associated with the 4- to 5-day estrous cycle decelerates age-related decreases in the frequency of luteinizing hormone (LH) pulses to assess whether hormonal milieu influences the rate of aging of the pulse generator. We determined the percentage of rats exhibiting pulsatile LH secretion, mean LH levels, and amplitude and frequency of LH pulses in seven groups of ovariectomized (OVX) rats. Young (3-4 mo), middle-aged (8-10 mo), and old (18-22 mo) virgin rats, ovariectomized 4 wk (4WK-OVX) prior to experimentation, were used to determine the effect of age. The effect of long-term ovarian hormone deprivation was tested by ovariectomizing rats at 2-3 mo of age and using them when they were middle-aged (8-10 months) or old (18-22 mo). The effect of deprivation of cyclic increases in ovarian hormones associated with repeated estrous cycles was tested by using retired breeder (RB) rats that had been ovariectomized 4 wk prior to experimentation. Each rat was implanted with a right atrial cannula and bled the next day at 10-min intervals for 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)     

Roles of estradiol and gonadotropin-releasing hormone in controlling negative and positive feedback associated with the luteinizing hormone surge in ovariectomized pigs.

Ovariectomized gilts (n = 63) were given estradiol benzoate (estradiol), antiserum to neutralize endogenous GnRH, and pulses of a GnRH agonist (GnRH-A) to stimulate release of LH. GnRH-A was given as 200-ng pulses hourly from 0 to 54 h and as 100- or 200-ng pulses every 30 or 60 min from 54 to 96 h after estradiol. Estradiol alone suppressed LH from 6 to 54 h and elicited an LH surge that peaked at 72 h. When GnRH-A was given every 30-60 min from 0 to 96 h, estradiol suppressed LH for 6-12 h, but then LH returned to pre-estradiol concentrations. When pulses of GnRH-A were given only between 54 and 96 h after estradiol, the surge of LH was related positively to dose and frequency of GnRH-A. We conclude that 1) estrogen acts at the hypothalamus to inhibit release of GnRH for 54 h and then causes a synchronous release of GnRH; 2) estrogen acts at the pituitary to block its response to GnRH for 6-12 h and enhances the accumulation of releasable LH; and 3) magnitude of the LH surge is dependent on the amount of GnRH stimulation.     

Effects of acute ovariectomy on anterior pituitary gland follicle-stimulating hormone and luteinizing hormone secretion in the metestrous rat

Changes at the anterior pituitary gland level which result in follicle-stimulating hormone (FSH) release after ovariectomy in metestrous rats were investigated. Experimental rats were ovariectomized at 0900 h of metestrus and decapitated at 1000, 1100, 1300, 1500, 1700 or 1900 h of metestrus. Controls consisted of untreated rats killed at 0900 or 1700 h and rats sham ovariectomized at 0900 h and killed at 1700 h. Trunk blood was collected and the serum assayed for FSH and luteinizing hormone (LH) concentrations. The anterior pituitary gland was bisected. One-half was used to assay for FSH concentration. The other half was placed in culture medium for a 30-min preincubation and then placed in fresh medium for a 2-h incubation (basal FSH and LH release rates). The basal FSH release rate and the serum FSH concentration rose significantly by 4 h postovariectomy and remained high for an additional 6 h. The basal FSH release rate and the serum FSH concentration correlated positively (r=0.71 with 72 degrees of freedom) and did not change between 0900 and 1700 h in untreated or sham-ovariectomized rats. In contrast, the serum LH concentration and the basal LH release rate did not increase after ovariectomy. Ovariectomy had no significant effect on anterior pituitary gland FSH concentration. The results suggest that the postovariectomy rise in serum FSH concentration is the result, at least in part, of changes which cause an increase in the basal FSH secretion rate (secretion independent of the immediate presence of any hormones of nonanterior pituitary gland origin). The similarities between the selective rises in the basal FSH release rate and the serum FSH concentration in the ovariectomized metestrous rat and in the cyclic rat during late proestrus and estrus raise the possibility that an increase in the basal FSH release rate may be involved in many or all situations in which serum FSH concentration rises independently of LH.     

Circulating radioimmunoassayable inhibin during periods of transient follicle-stimulating hormone rise: secondary surge and unilateral ovariectomy

We have measured changes in circulating immunoreactive (ir-) inhibin in male and female rats using an RIA with an antiserum raised against porcine inhibin alpha (1-26)-Gly-Tyr. The same synthetic peptide was used for standards and for the preparation of tracer. Serum ir-inhibin levels were significantly higher in intact female than in intact male rats (p less than 0.001). Immunoreactive inhibin was significantly reduced in both sexes 24 h after bilateral gonadectomy (p less than 0.0001). Unilateral ovariectomy (ULO) of female rats on metestrus caused a transient decrease in serum inhibin 8 h after surgery, but levels were not significantly different from those of sham-operated controls at later times after surgery. Increases in serum FSH and LH were observed for 8-18 h after ULO. Serum ir-inhibin levels were also measured on the early morning of estrus during the secondary FSH surge. At this time, ir-inhibin levels were low, while FSH levels were high and LH levels were low. These results show that serum ir-inhibin levels in rats are decreased at times when serum FSH levels are high.     

Independence of progesterone blockade of the luteinizing hormone surge in ewes from opioid activity at naloxone-sensitive receptors.

Fifteen ovariectomized ewes were treated with implants (s.c.) creating circulating luteal progesterone concentrations of 1.6 +/- 0.1 ng ml-1 serum. Ten days later, progesterone implants were removed from five ewes which were then infused with saline for 64 h (0.154 mol NaCl l-1, 20 ml h-1, i.v.). Ewes with progesterone implants remaining were infused with saline (n = 5) or naloxone (0.5 mg kg-1 h-1, n = 5) in saline for 64 h. At 36 h of infusion, all ewes were injected with oestradiol (20 micrograms in 1 ml groundnut oil, i.m.). During the first 36 h of infusion, serum luteinizing hormone (LH) concentrations were similar in ewes infused with saline after progesterone withdrawal and ewes infused with naloxone, but with progesterone implants remaining (1.23 +/- 0.11 and 1.28 +/- 0.23 ng ml-1 serum, respectively, mean +/- SEM, P greater than 0.05). These values exceeded circulating LH concentrations during the first 36 h of saline infusion of ewes with progesterone implants remaining (0.59 +/- 0.09 ng ml-1 serum, P less than 0.05). The data suggested that progesterone suppression of tonic LH secretion, before oestradiol injection, was completely antagonized by naloxone. After oestradiol injection, circulating LH concentrations decreased for about 10 h in ewes of all groups. A surge in circulating LH concentrations peaked 24 h after oestradiol injection in ewes infused with saline after progesterone withdrawal (8.16 +/- 3.18 ng LH ml-1 serum).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of monensin and suckling on the GnRH induced luteinizing hormone surge and the effect of monensin on the postpartum interval in Brangus cows

Twenty-seven fall calving Brangus cows were randomly allotted to one of four treatment groups: nonsuckled monensin (NSM), suckled monensin (SM), nonsuckled control (NSC), and suckled control (SC). Cows were group fed 1.82 kg/hd/day concentrate and Coastal bermuda grass hay $\text{ad}$$\text{libitum}$. Monensin cows received 200 mg monensin/hd/day in the concentrate. At 0800 hr on day 21 postcalving, the calves were separated from the cows. Suckled monensin and SC cows were allowed to suckle their calves for 30 min at 6-hr intervals. Nonsuckled monensin and NSC cows were not suckled. Calves were given free access to the cows after 1400 hr on day 22 postpartum. At 0800 hr on day 22 postpartum, a blood sample was collected. A 100 μg GnRH challenge was administered IM at 0801 hr. Blood samples were collected at 15-min intervals for 6 hr postinjection. Changes in body weight and body condition from day 21 postpartum to the day of first estrus were not different (P>0.10) by dietary treatment. Monensin cows consumed 10.7% less hay than did the control cows. Serum luteinizing hormone (LH) following GnRH was greater (P<0.005) in suckled than nonsuckled cows. Control cows released more (P<0.005) LH in response to GnRH than did the monensin cows. The postpartum interval (to first estrus) for the monensin cows (92.4±14.7 days) was shorter (P<0.025) than the controls (138.5±9.5 days). A greater proportion (P<0.005) of the monensin cows (8 of 14) exhibited estrus by 90 days postpartum compared to the control cows (0 of 13). Monensin and suckling appear to exert independent and agonistic influences on pituitary function in the postpartum beef cow.     

Vasopressin regulation of the proestrous luteinizing hormone surge in wild-type and Clock mutant mice

In the female mouse, ovulation and estrous cyclicity are under both hormonal and circadian control. We have shown that mice with a mutation in the core circadian gene Clock have abnormal estrous cycles and do not have a luteinizing hormone (LH) surge on the afternoon of proestrus due to a defect at the hypothalamic level. In the present study, we tested the hypotheses that vasopressin (AVP) can act as a circadian signal to regulate the proestrous release of LH, and that this signal is deficient in the Clock mutant. We found that Avp expression in the suprachiasmatic nucleus (SCN) and AVP 1a receptor (Avpr1a) expression in the hypothalamus is reduced in Clock mutant mice compared to wild-type mice. Intracerebroventricular (i.c.v.) injection of AVP on the afternoon of proestrus is sufficient to induce LH secretion, which reaches surge levels in 50% of Clock mutant mice. The effect of AVP on the Clock mutant LH surge is mediated by AVPR1A, as co-infusion of AVP and an AVPR1A-specific antagonist prevents AVP induction of LH release, although infusion of an AVPR1A antagonist into wild-type mice failed to prevent a proestrous LH surge. These results suggest that reduced hypothalamic AVP signaling plays a role in the absence of the proestrous LH surge in Clock mutant mice. The results also support the hypothesis that AVP produced by the SCN may be a circadian signal that regulates LH release.     

The effects of luteinizing hormone, oestrogen and ovariectomy on the agonistic behaviour of female Quelea quelea

Previous work with male Quelea showed that agonistic behaviour in relation to individual distance is controlled by luteinizing hormone (LH), rather than by testosterone, and that males are more aggressive than females. Experiments with female groups are reported which show that: (a) LH injections increase aggressive encounter frequency; (b) ovariectomy in the breeding season (but not outside it) also increases encounter frequency; and (c) oestrogen injections decrease encounter frequency. The effects of LH were shown to be specific to agonistic responses rather than mediated through changes in activity. Correlations between changes in natural hormone levels and encounter frequency support the injection findings. These results are consistent with the hypothesis that LH controls aggressive encounters over individual distance in the female as in the male and that oestrogenic inhibition of this LH-mediated aggressiveness is a cause of female subordination and the lower encounter frequency found in female groups. The annual cycle of encounter frequency is described and the significance of different systems of hormonal control is discussed.     

Opioidergic control of luteinizing hormone release in the female rabbit: influence of ovariectomy and steroid replacement on pulsatile secretion

The influence of ovariectomy and steroid replacement on naloxone-induced changes in pulsatile secretion of luteinizing hormone (LH) in the female rabbit was examined. Blood samples were taken every 5 min through an indwelling catheter in the rabbit ear artery, and plasma was stored until assayed for LH by established radioimmunoassay procedures. In the intact animal, saline injection had no effect on LH secretion. Although naloxone (10 mg/kg) caused a 7-fold increase in mean LH pulse amplitude by 30 min after injection, this increase was not statistically significant because 5 of 11 animals did not respond. In animals ovariectomized 48 h previously, naloxone significantly increased LH concentration by 194% at 23 min after injection. When long-term ovariectomized rabbits were treated with estradiol benzoate and then were given naloxone, no significant increase in LH was observed, although many animals did respond. Treatment of long-term ovariectomized rabbits with 1 microgram estradiol benzoate and 100 micrograms progesterone or 1 mg testosterone propionate on Days 1 and 3 and naloxone on Day 4 resulted in a significant increase in LH 19-24 min later. Although there was an increase in pulse amplitude, no change was detected in pulse frequency after naloxone. These data suggest that the hypothesis of steroid-opioid coupling in the control of LH secretion is not applicable to the female rabbit.     

Effects of time after ovariectomy, season and oestradiol on luteinizing hormone and follicle-stimulating hormone secretion in ovariectomized ewes.

During the breeding season, five groups of three ewes were implanted at ovariectomy with 0.36, 0.5, 1.0 and 6.0 cm oestradiol implants or implants containing no steroid. Eleven days after receiving implants, blood samples were taken every 10 min for 6 h; implants were then removed. Treatments were repeated three times during each of two consecutive breeding seasons and four times during the intervening anoestrus. In ovariectomized ewes without steroid treatment, luteinizing hormone (LH) pulse frequency increased from early to mid-breeding season, decreased to a minimum at mid-anoestrus and increased to reach a maximum at the mid-point of the second breeding season, subsequently declining. LH pulse amplitude was inversely related to frequency. Basal serum LH concentrations decreased gradually from the first breeding season to reach a minimum at mid-anoestrus and gradually increased to reach a maximum at the end of the second breeding season. Mean serum LH and follicle-stimulating hormone (FSH) concentrations were higher at the end of the second breeding season compared with the beginning of the first breeding season. All parameters of gonadotrophin secretion were decreased much more by oestradiol during the anoestrus than during the breeding season. LH pulse frequency was decreased during anoestrus and at high oestradiol concentrations during the first breeding season. Apart from LH pulse amplitude, the decreases in all parameters of gonadotrophin secretion were less during the second compared with the first breeding season. The minimum effective dose of oestradiol required to decrease mean and basal serum concentrations of LH during anoestrus was lower than in the breeding season. The minimum effective dose of oestradiol required to decrease mean serum concentrations of FSH was lower in the first compared with the second breeding season. Oestradiol depression of LH pulse amplitude and mean serum concentrations of LH and FSH showed a dose dependency during the breeding season. During anoestrus dose dependency was seen for basal concentrations of LH and mean serum concentrations of LH and FSH. We conclude that significant chronic changes in gonadotrophin secretion occur in the ewe with time after ovariectomy. Sensitivity to oestradiol also changes, and the effects of oestradiol are not always dose dependent. We suggest that the circannual pattern of LH pulse frequency and basal LH secretion are directly linked to the circannual cycle of photoperiod.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of suckling and ovariectomy on the control of luteinizing hormone secretion during the postpartum period in beef cows

Twenty-two mature pluriparous beef cows were randomly assigned to one of six treatments in a 2 X 3 factorial experiment in order to study the role of suckling and ovarian factors on control of the tonic and episodic release of luteinizing hormone (LH). Twelve cows remained intact (INT) and 10 were ovariectomized (OVX) within 4 days following the day of parturition (Day 0). The suckling intensities were nonsuckled (0), suckled once daily for 30 min (1) and suckled ad libitum by two calves (2). Blood samples were collected at 15-min intervals for 6 h weekly, from Days 6 to 76 postpartum. The postpartum intervals to initiation of ovarian luteal function were 31 +/- 3, 41 +/- 4 and 67 +/- 1 days (means +/- SEM) for INT cows with 0, 1 and 2 suckling intensities, respectively. Mean LH concentrations and frequency of LH pulses increased as time of ovulation approached in INT cows. In OVX animals, both mean LH concentrations and frequency of LH pulses increased as time postovariectomy progressed. No differences were detected in mean LH concentrations or frequency of LH pulses between the two suckled OVX groups. Mean LH in the OVX-0 cows was greater on Days 13, 20 and 27 postpartum when compared to the respective days in suckled OVX cows. Frequency of LH pulses tended to be lower (P less than 0.10) in both suckled OVX groups when compared with OVX-0 cows from Day 6 to Day 55 postpartum. It is postulated that suckling and ovarian factors act together during the postpartum period to suppress LH levels and frequency of LH pulses in beef cows.     

Guanidination of ovine luteinizing hormone and effects on activity.

The free amino groups in oLH, oLHalpha and oLHbeta were guanidinated by O-methylisourea. The epsilon-NH2 groups of lysine residues reacted bo substitute these positions in the sequence with the more basic homoarginine residue. The alpha-NH2 groups did not react under the conditions used. Guanidinated oLH or the products of guanidinated oLHalpha + native oLHbeta or guanidinated oLHalpha + guanidinated oLHbeta were inactive in two bioassay systems. Native oLHalpha + guanidinated oLHbeta, however, showed potencies of 39% to 55% of that observed with the native subunit recombinant or native oLH. Possible structural implications for hormone-receptor site interactions are discussed.     

Nutritional anestrus in beef cows: effects of body condition and ovariectomy on serum luteinizing hormone and insulin-like growth factor-I

The objectives of this experiment were to determine if a postcastration increase in concentrations of LH occurs in nutritionally anestrous beef cows and to examine the relationship between body energy reserves and secretion of LH and insulin-like growth factor-I (IGF-I). Nonpregnant, nonlactating, Hereford cows were fed to maintain (M) body weight (BW), body condition score (BCS), and normal estrous cycles (n = 5) or were fed a restricted (R) diet for 26 wk to lose BW and BCS and to become anestrus (n = 10). At 5-7 wk after the initiation of anestrus, R cows were randomly allotted to be ovariectomized (OVX) via flank incision (n = 5) or to remain intact (INT, n = 5). OVX was performed when R cows became anestrous. All M cows were OVX. Serum was collected frequently the day before and during the first 10 days after OVX, and concentrations of progesterone, estradiol, LH and IGF-I were quantified. On Day 10 after OVX, 1 mg of estradiol was injected into 3 cows from each group and serum was collected for 30 h. After OVX, there was a treatment-by-day effect for mean serum LH and IGF-I concentrations. Concentrations of LH increased (p less than 0.01) and concentrations of IGF-I decreased (p less than 0.05) in M-OVX cows when compared with R-OVX and R-INT cows. Concentrations of LH and IGF-I were similar for R-OVX and R-INT cows. The number of LH pulses was similar for M and R cows.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of ovariectomy or force feeding on the plasma concentrations of prolactin and luteinizing hormone in incubating turkey hens

The effect of ovariectomy (OVX) on plasma concentrations of prolactin (PRL) and luteinizing hormone (LH) in incubating turkey hens was studied. Neither the sham-operated nor the OVX hens exhibited any change in the pattern of incubation behavior as a result of the surgery. Plasma concentrations of estradiol decreased to less than approximately 3 pg/ml by 2 days after surgery in the OVX hens. There were no significant differences in plasma levels of PRL between the sham-operated and OVX hens throughout the study. The concentration of PRL did not change in either the sham-operated or OVX hens and was maintained at high levels after surgery and during incubation of the eggs. By 2 days after hens were placed into cages, plasma levels of PRL significantly decreased and were maintained at low levels in both groups. The concentration of LH did not change in either group during the two wk after surgery when the hens were incubating eggs. After the hens were placed into cages, the concentration of LH increased in the OVX hens and was maintained at significantly higher levels than in the sham-operated hens. By contrast, the concentration of LH increased within 4 days after OVX of out-of-lay but nonincubating hens. The delay in the postcastration increase in plasma level of LH in the OVX hens was not associated with anorexia of incubating hens, since plasma levels of LH were not affected by force-feeding unless plasma levels of PRI were suppressed by nest deprivation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in luteinizing hormone-releasing hormone content of discrete hypothalamic areas associated with spontaneous and induced preovulatory luteinizing hormone surges in the domestic hen

It is widely assumed that luteinizing hormone-releasing hormone (LHRH) neuronal activation is involved in the preovulatory surge of LH in the hen. In addition, this LH surge may be initiated by ovarian progesterone (P4) release. Thus, spontaneous and P4-induced LH surges should be associated with acute changes in LHRH content of discrete hypothalamic areas associated with LHRH cell bodies and/or LHRH axon terminals. Medial preoptic area (mPOA) and infundibulum (INF) LHRH content was measured by radioimmunoassay at intervals before, at, and following peak LH levels of a spontaneous preovulatory surge of LH, as well as when this surge was advanced by P4 administration in laying hens. Nonlaying birds served as additional controls. Levels of serum LH, P4, 17 beta-estradiol and pituitary LH were also measured. Increased (P less than 0.05) LHRH content in mPOA without changes in the INF are associated with peak serum LH levels of the spontaneous LH surge. By contrast, decreased (P less than 0.05) LHRH content in both mPOA and INF is associated with peak serum LH levels when the spontaneous surge was advanced 8 h by P4 administration to laying hens. Medial preoptic area and INF LHRH contents were significantly lower (P less than 0.05) in nonlaying than in laying hens.(ABSTRACT TRUNCATED AT 250 WORDS)