Μg LH-RH Research Articles

165 EFFECTS OF AGE, HORMONES AND HIBERNATION ON BREEDING SUCCESS IN BOREAL TOADS (BUFO BOREALIS)

The global amphibian extinction crisis has stimulated interest in captive breeding programs for this diverse taxa. The goals of this study were to test the effects of exogenous hormone injections (LHRH and hCG) and hibernation on breeding behavior and gamete release by the boreal toad, a temperate species. The 5-year study was initiated with 77 toadlets. Each year, a subset of female and/or male toads was hibernated for 5 months at 4°C. The remaining toads were maintained in a lab receiving 12 h of light daily and ample food and water. Within 48 h of removal from hibernation, toads were paired with hibernated or non-hibernated mates. All toads were weighed and pairs were randomly assigned to treatments. Toads were injected IP with 6 μg LHRH, 250 IU hCG, or saline control and observed for amplexus and egg production. Some treatment groups received a second hormone injection if eggs were not produced within 48 h. Eggs were counted and transferred to aquariums for tadpole and toadlet development. During years 1 to 3, sperm production was assessed in male toads by sampling tank water or urine samples after injections. Data were analyzed using unpaired t-tests and chi-square analyses. In year 1, only 19% of pairs overall exhibited amplexus, none of the males produced sperm and none of the females produced eggs. In year 2, only male toads injected with LHRH exhibited amplexus, and it was more prevalent (P < 0.05) in those that were hibernated than non-hibernated (54.0% and 33.3%, respectively). Percentage of pairs in amplexus in years 2 and 3 (56.9% and 100%) was greater (P < 0.05) than in year 1. Only one and two females produced eggs in years 2 and 3, respectively. In contrast, most hibernated (87.5%) and non-hibernated (75%) males produced sperm. In year 4, eight females produced eggs, but two of these died egg-bound. Interestingly, more (P < 0.05) non-hibernated (7/10) than hibernated (1/10) females produced eggs despite no differences (P ≥ 0.05) in proportion of pairs amplexing or time spent in amplexus between groups. Mean (±SD) weight of female toads producing eggs (58.9 ± 11.9 g) was greater (P < 0.05) than that for non-producing females (43.6 ± 7.0 g). Similarly, 4/7 non-hibernated females produced eggs in year 5, and their weights averaged (58.8 ± 8.3 g). All eggs were produced by females injected a single time with LHRH. Number of eggs per female varied (141–3307), and percentage of eggs developing to tadpoles was low (0–36.5%), but tadpoles were capable of developing into adult toads. In conclusion, two-year-old male boreal toads are mature, exhibiting amplexus and releasing sperm in response to LHRH injections. Females appear to mature at four years of age, and eggs are more likely to be produced by heavier females. Therefore, to enhance breeding success, males should be hibernated and injected with LHRH. In contrast, better productivity in females may be achieved by improving their body condition instead of subjecting them to winter hibernation prior to LHRH injection. Supported by: AZA Conservation Endowment Fund and Colorado Division of Wildlife.

Alteration of gonadotrophin and steroid hormone release, and of ovarian function by a GnRH antagonist in gilts

This study examined the impact of the gonadotrophin-releasing hormone (GnRH) antagonist Antarelix™ on LH, FSH, ovarian steroid hormone secretion, follicular development and pituitary response to LHRH in cycling gilts. Oestrous cycle of 24 Landrace gilts was synchronised with Regumate ® (for 15 days) followed by 800 IU PMSG 24 h later. In experiment 1, Antarelix™ ( n=6 gilts) was injected i.v. (0.5 mg per injection) twice daily on four consecutive days from day 3 to 6 (day 0=last day of Regumate ® feeding). Control gilts ( n=6) received saline. Blood was sampled daily, and every 20 min for 6 h on days 2, 4, 6, 8 and 10. In experiment 2, gilts ( n=12) were assigned to the following treatments: Antarelix™; Antarelix™ + 50 μg LHRH on day 4; Antarelix™ + 150 μg LHRH on day 4 or control, 50 μg LHRH only on day 4. Blood samples were collected daily and every 20 min for 6 h on days 2, 4 and 6 to assess LH pulsatility. Ovarian follicular development was evaluated at slaughter. Antarelix™ suppressed ( P<0.05) serum LH concentrations. The amount of LH released on days 4–9 (experiment 1) was 8.80 versus 36.54 ng ml −1 (S.E.M.=6.54). The pattern of FSH, and the preovulatory oestradiol rise was not affected by GnRH antagonist. Suppression of LH resulted in a failure ( P<0.05) of postovulatory progesterone secretion. Exogenous LHRH (experiment 2) induced a preovulatory-like LH peak, however in Antarelix™ treated gilts the LH surge started earlier and its duration was less compared to controls ( P<0.01). Furthermore, the amount of LH released from day 4 to 5 was lower ( P<0.01) in Antarelix™, Antarelix™ + 50 and Antarelix™ + 150 treated animals compared to controls. No differences were estimated in the number of LH pulses between days and treatment. Pulsatile FSH was not affected by treatment. Mean basal LH levels were lower ( P<0.05) after antagonist treatment compared to controls. Antarelix™ blocked the preovulatory LH surge and ovulation, but the effects of Antarelix™ were reduced by exogenous LHRH treatment. The development of follicles larger than 4 mm was suppressed ( P<0.05) by antagonist treatment. In conclusion, Antarelix™ treatment during the follicular phase blocked preovulatory LH surge, while FSH and oestradiol secretion were not affected. Antarelix™ failed to alter pulsatile LH and FSH secretor or pituitary responsiveness to LHRH during the preovulatory period.

Lack of suppressive action of luteal factors from sheep corpus luteum on LH response to exogenous LHRH in ovariectomized, pregnant and post-partum ewes.

In vivo studies have provided evidence of a non-steroidal factor from ovine corpora lutea (CL) of pregnancy called LH-release inhibiting factor (LH-RIF), which specifically inhibits tonic LH release without affecting FSH secretion. To study the possible pituitary site of action of LH-RIF and other factors from sheep CL of pregnancy, the LH response to LHRH was investigated in ovariectomized (OVX) ewes pretreated with ovine luteal extract (oLE) from CL of mid-pregnancy, and in pregnant and post-partum ewes from which the CL were removed at mid-pregnancy. In view of the fact that human follicular fluid (hFF) contains a non-steroidal factor, called gonadotrophin surge-attenuating factor, which attenuates the LHRH-induced LH release, it was clearly important to examine the LHRH-induced LH release in OVX ewes pretreated with oLE or hFF In experiment 1, the LH and FSH responses (the maximum LH and FSH concentrations, the time to maximum LH and FSH concentrations and the area under the LH and FSH response curves) to a single i.v. injection of 5 microg of the LHRH agonist buserelin was not significantly different between ewes pretreated with oLE and ewes pretreated with BSA. Although the LHRH-induced LH and FSH release was slightly attenuated in OVX ewes pretreated with hFF as compared with OVX ewes pretreated with BSA, the maximum LH and FSH concentrations and the area under the LH and FSH response curves were not significantly different between the two groups of ewes. In experiment 2, the LH responses to a single i.v. injection of 0.5 microg LHRH on days 80 and 100 of pregnancy were not significantly different between intact ewes and ewes from which the CL were removed on day 70 of pregnancy. In both groups of ewes the maximum LH concentration and the area under the LH response curve were significantly lower (P <0.02) on day 100 than on day 80 of pregnancy. In experiment 3, the LH responses to a single i.v. injection of 50 microg LHRH on day 140 of pregnancy and on day 10 post-partum were not significantly different between intact ewes and ewes from which the CL were removed on day 70 of pregnancy. In both groups of ewes the maximum LH concentration and the area under the LH response curve were significantly lower (P <0.01) on day 140 of pregnancy than on day 10 post-partum. These experiments provide evidence for a lack of suppressive action of luteal secretory products from the ovine CL of pregnancy on the pituitary LH response to LHRH in OVX, pregnant and post-partum ewes.

Mediation by nitric oxide of LH-RH-stimulated gonadotropin secretions in human subjects

In order to establish whether nitric-oxide (NO) participates in the regulation of gonadotropin secretion in humans, seven normal men were treated with a placebo (normal saline) or the NO synthase inhibitor l-name, given at doses (40 μg/kg injected plus 50 μg/kg infused i.v.) previously found to be unable to change blood pressure. Experiments were carried out either in basal conditions or during stimulation of gonadotropin secretion with an intravenous injection of 100 μg LH-RH. The administration of l-name was unable to change the basal secretion of FSH and LH. In contrast, l-name significantly reduced both FSH and LH increments induced by LH-RH. These data fail to provide evidence of NO involvement in regulation of basal gonadotropin secretion. In contrast, the inhibitory effect of l-name on LH-RH-induced LH and FSH secretion suggests the modulation by NO of the gonadotropin releasing action of LH-RH.

Differential control of luteinizing hormone and follicle-stimulating hormone secretion by luteinizing hormone-releasing hormone pulse frequency in man.

To test the hypothesis that the frequency of pulsatile LHRH stimulation can differentially control LH and FSH secretion in man, we administered low doses of LHRH in pulsatile fashion in several different regimens to men with idiopathic hypogonadotropic hypogonadism (IHH) and presumed endogenous LHRH deficiency. In study 1, four men with IHH received a constant amount of LHRH per day in three different frequencies. After an initial 7-day period of LHRH (5.0 micrograms every 2 h), the men received 2.5 micrograms every 1 h and 7.5 micrograms every 3 h, each for 4 days, in varying order. Frequent blood samples were obtained before LHRH administration and at the end of each regimen. Before LHRH administration, mean serum FSH and LH levels were low [28 +/- 3 (+/- SEM) and 6 +/- 2 ng/mL, respectively], and they increased into the normal adult male range during LHRH treatment. As the frequency of LHRH administration decreased from every 1 to 2 to 3 h, serum FSH levels progressively increased from 99 +/- 33 to 133 +/- 34 to 181 +/- 58 ng/mL (P less than 0.05). Serum LH levels (34 +/- 6, 33 +/- 6, and 34 +/- 5 ng/mL) were significantly higher than those before LHRH administration and did not differ significantly among the three regimens. Total serum testosterone (T), estradiol, and free T levels were increased by LHRH, but were not significantly different during the three regions of LHRH administration. In study 2, three men with IHH received the same amount of LHRH per dose, given in two different pulse frequencies; 2.5 micrograms LHRH were administered in frequencies of every 0.5 h and every 1.5 h, each for 4 days, in varying order. During the 0.5 h frequency, the mean serum FSH level was 42 +/- 13 ng/mL, and it rose to 80 +/- 19 ng/mL during the 1.5 h frequency (P less than 0.05). Corresponding mean serum LH levels were 25 +/- 5 and 27 +/- 4 ng/mL. Serum T and estradiol levels were not significantly different during the two LHRH regimens. We conclude that the frequency of LHRH stimulation can differentially control FSH and LH secretion by the human pituitary gland, and the pattern of hormonal stimulation may be a determinant of target organ response.

Effects of an LH-releasing hormone antagonist on the secretion of LH, FSH, prolactin and ovarian steroids at different stages of the luteal phase in the stumptailed macaque (Macaca arctoides).

The role of the pituitary gonadotrophins in controlling luteal function in the stumptailed macaque has been investigated by examining profiles of serum concentrations of LH, FSH, progesterone and oestradiol in daily blood samples from 13 monkeys during the menstrual cycle, and in blood samples taken at hourly intervals between 09.00 and 21.00 h on different days of the luteal phase in 13 cycles. The effects of acute withdrawal of gonadotrophins was investigated by administering a single injection of 300 micrograms LHRH antagonist/kg body weight at different stages of the luteal phase during 28 cycles. Although there were high basal values and marked fluctuations of bioactive LH during the first 4 days after the LH peak, progesterone profiles showed no corresponding short-term changes, there being a slow and steady rise in progesterone concentrations during the sampling periods. After day 5, basal LH secretion decreased, but high amplitude LH pulses were identified which were associated with episodes of progesterone secretion. Administration of the LHRH antagonist caused a suppression of bioactive LH and progesterone concentrations at all stages of the luteal phase, although some basal secretion of progesterone was maintained through the 24-h period of effective antagonist gonadotroph blockade. Luteal function recovered apparently normally in all monkeys treated in the early-mid-luteal phase. Serum concentrations of FSH and oestradiol fluctuated comparatively less during the 12-h sampling periods, and the antagonist had less suppressive effects on the concentrations of these hormones. The LHRH antagonist had no apparent effect on prolactin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypothalamic site of progesterone action on gonadotropin release.

Tonic gonadotropin secretion was monitored at 20 min intervals for a total of 9 hours in 3 female volunteers during the mid-luteal phase of an ovulatory cycle. This control period was followed by repeated LH-RH stimulation (12 micrograms LH-RH as i.v. bolus once every hour for another 5 hours). During the control period spontaneous albeit low-frequent pulsatile secretion was observed for LH (a pulse occurring once every 3-8 hours) but not for FSH. While intermittent exogenous LH-RH stimulation was being performed at circhoral LH-RH pulse frequency pulsatile gonadotropin release was established at synchronous episodicity and systemic gonadotropin levels consecutively increased. These data provide indirect evidence that the pituitary gland is not rendered refractory to LH-RH by luteal progesterone secretion but readily responds to LH-RH stimuli even when these simulate a follicular phase LH-RH pulse frequency. Thus, it is concluded that spontaneous pulsatile LH release at low frequency during the luteal phase of the cycle reflects low frequent LH-RH discharges from the hypothalamus. Underlying mechanisms are discussed.

Temporal difference of thyrotropin-releasing hormone in prevention of testicular regression in golden hamsters exposed to short photoperiods: possible involvement of beta-endorphin.

Male golden hamsters were exposed to long photoperiod or short photoperiod (SP) and injected with 1 microgram TRH and/or 1 microgram LHRH at lights on (LO) or lights off (LX) for a total of 8 weeks. Both TRH and LHRH prevented testicular regression if they were injected at LO. Injected at LX, TRH did not prevent testicular regression, and LHRH was only partially effective. Plasma beta-endorphin levels were significantly higher in groups with atrophic testes. These results indicate that TRH like LHRH can prevent SP-induced testicular regression in hamsters by some unknown mechanism and that beta-endorphin may be involved in the control of testicular function in hamsters.

The effect of combined oral contraceptive steroids on the gonadotropin responses to LH-RH in lactating women with regular menstrual cycles resumed

The effect of combined oral contraceptive steroids upon pituitary response to stimulation with 100 μg LH-RH was studied in both non-puerperal and lactating women with regular menstrual cycles. Serum prolactin concentration was 14.20 ng/ml in non-puerperal women whereas it was 39.37 ng/ml in lactating women. A comparability was shown in the LH response to LH-RH in non-puerperal women and lactating women. FSH response to LH-RH, however, was significantly exaggerated in lactating-menstruating women as compared to that of non-puerperal women. Combined oral contraceptive steroids lowered basal levels of LH and FSH in non-puerperal women and lactating women although the difference was not statistically significant in non-puerperal women. The LH and FSH maximal responses to LH-RH were significantly diminished in both non-puerperal and lactating women on combined oral contraceptives. There was, however, no difference in the mean LH or FSH responses between non-puerperal women and lactating women. Combined oral contraceptive steroids used in this study seemed to suppress ovulation by decreasing the pituitary responsiveness to LH-RH in lactating-menstruating women as well as in normally menstruating women.

Reproductive hormone changes during weight gain in male anorectics.

Plasma LH, FSH, testosterone and sex-hormone-binding globulin have been measured in a total of ten male anorectics. There was no significant correlation between body weight and FSH levels or body weight and SHBG levels. Both LH and testosterone concentrations were significantly correlated with body weight. They were well below the adult normal range at low body weight and rose with weight gain although in many cases neither hormone reached normal levels at target weight. The plasma LH and FSH response to 50 micrograms LHRH was measured in five male anorectics on twelve occasions, and compared with the responses of twelve normal adult males. The anorectic patients showed a FSH response which was normal on eleven occasions and slightly raised on one occasion. The LH response was below normal at weights below 40 kg, exaggerated between 45 kg and 50 kg and within normal limits at other weight ranges. These results are compared with previous findings in female anorectics.

Effect of prolonged administration of small doses of LH-RH and LH-RH analogue [D-Ser (But) 6] Des Gly-NH 210 ethylamide on the release of LH and induction of ovulation in mid-anoestrous ewes

A natural process of LH release and induction of ovulation in anoestrous ewes was simulated by prolonged administration of small doses of LH-RH and its analogue [D-Ser(But) 6] Des Gly-NH 2 10 ethylamide. In the first series of experiments on 40 Merino ewes infusions of LH-RH were made into the maxillaris interna artery for 6 consecutive days for 6 h each day. Total doses of 24.0, 26.0, 28.0 and 32.0 μg per animal of varying and progressively increasing daily quantities of the hormone were administered in groups I, II, III and IV, respectively. In group V the animals were infused with a total dose of 28.0 μg LH-RH and injected additionally i.m. with 3.0 μg 17β-oestradiol on days 4 and 5 of the infusion of LH-RH. Ovulation did not occur earlier than days 4, 5 and 6 after the beginning of infusions. The highest number of positive reactions occurred in group IV ( 8 10 ) and in group V ( 7 8 animals). The pattern of LH peaks in general was correlated with the time of ovulations. The LH concentrations of the preovulatory peaks in experimental ewes were mostly lower than those in naturally ovulating animals. The corpora lutea were functional during the first 7 days after ovulation. In the second series of experiments on 26 Merino ewes the LH-RH analogue [D-Ser -(But) 6] Des Gly-NH 2 10 ethylamide was injected i.m. or i.a. for 6 consecutive days. Total doses of 15.5, 9.5 and 7.5 μg of the analogue per animal, administered at varying and progressively increasing daily doses in respective groups, induced several surges of LH in the same individuals for 2 or even 3 consecutive days. Corpora lutea and degenerating follicles in the form of cysts were found in the ovaries of animals of these groups. Very small daily doses ranging from 0.1 μg administered during the first 3 days, to 1.5 μg on day 5 of the treatment, released one surge of LH on day 5 of the treatment in all individuals with peaks ranging from 30.0 to 58.0 ng/ml and induction of ovulation with almost normal luteal function. On the basis of these experiments it is suggested that the evaluation of the effect of active substance (LH-RH or its analogue), its suitability and application of rightly chosen doses to induce the full physiological process of ovulation should be based not only on the release of LH and luteal function but also on tests of the ability of the released ovum to undergo fertilization and its further development.

Lack of effect of melatonin on the pituitary response to LH-RH in the ewe.

Administration of 100 micrograms LH-RH to cyclic ewes gave peak values of circulating LH similar to those found at the time of oestrus although the duration of elevated LH levels was less. There was also considerable individual variation in response. Pretreatment or simultaneous administration with melatonin (500 micrograms or 2 mg) did not alter the individual response to LH-RH.

Facilitation of sexual receptivity in the rat by an ovulation-inhibiting analog of LHRH

An LHRH analog known to inhibit ovulation the rat ([N-Ac-Phe 1, D-p-Cl-Phe 2, D-Trp 3,6]LHRH) was tested for its effects on sexual receptivity. The dose of 500 ng/rat was found in dose-response experiments to be most active and was further investigated for its behavioral effects in rats treated with either estrogen or estrogen plus progesterone. The analog significantly facilitated the behavior of rats in regimens producing low [estradiol benzoat (EB) (2μg)] and intermediate [EB (2 μg) plus progesterone (2.5 mg)] levels of sexual behavior. In rats given regimens producing high behavioral scores [EB (5 μg) plus progesterone (1 mg)], the peptide did not reduce mating behavior. In the same experiment, rats given EB (5 μg) but not progesterone showed significantly higher scores after the LHRH analog only if they had been designated ”responders” by a previous screening test with 1 μg LHRH. These results demonstrate that in animals showing low, intermediate, or high levels of sexual behavior, the LHRH analog can affect mating behavior in a direction quite different from that exerted on pituitary reproductive functions.

Prolactin levels and the LH-response to synthetic LH-RH in the lactating sow

To determine the role of prolactin in the suppression of ovarian activity during lactation in the sow experiments were performed to investigate a possible inhibitory action of prolactin at the pituitary level. Therefore the LH-response to an intravenous injection of 25 μg synthetic LH-RH was measured in the 1st, 2nd and 3rd week of lactation. The compound was injected under high and low concentrations of prolactin in the peripheral blood, the latter achieved by removal of the piglets 6 h before administration of LH-RH. The results showed no difference in the effect of LH-RH injected at high or low prolactin levels. However, although the mean prolactin concentrations in the 1st, 2nd and 3rd week of lactation were similar, the results clearly demonstrated an increase in LH-response as lactation proceeds. The low responsiveness of the pituitary shortly post partum was also observed when the preparturient rise of prolactin was suppressed by treatment with bromoergocryptine. Injections of LH-RH in the last week of gestation given before and after the physiological increase of PRL, which occurred about 48 h before delivery, all showed low LH-response. It is obvious from the presented data that the LH-response to an intravenous injection of 25 μg LH-RH is in no way correlated with the prolactin levels at the time of treatment.

Hypothalamo-hypophyseal sensitivity to hormones in the hen. II. Plasma concentrations of LH, progesterone, and testosterone in response to peripheral and central injections of LHRH or testosterone.

Experiments were conducted to investigate changes in plasma LH, progesterone (P4), and testosterone (T) and the incidence of premature ovulation in response to peripheral and central injections of T or synthetic LHRH administered 14–12 h prior to the first ovulation in a sequence. Injection of 2.0 mg T (i.m.) induced premature ovulation in four of five hens. Plasma concentrations of LH and P4 in T-injected hens, compared with corresponding values from control hens, were significantly increased in all five birds by 90 min and reached highest concentrations by 180 and 240 min, respectively, following injection. Plasma T was increased to 19.88 ± 3.40 ng/ml (SEM) 30 min following injection of 2.0 mg T and slowly declined throughout the remaining sampling interval. There was no significant (P>0.05) dose relationship with respect to premature ovulation between 10.0 and 80.0 μg of centrally injected T. In an experiment in which hens served as their own controls and in which the control (vehicle) and 20 μg T intraventricular injections were assigned at random to each hen, T did not affect the incidence of ovulation or concentrations of plasma LH or P4, but plasma T concentration was increased significantly by the first sampling period (30 min) after injection, suggesting some leakage of T from the site of injection into the peripheral circulation. Four of the five hens injected i.v. with 20 μg LHRH responded with significant elevations in plasma LH, P4, and T by the first sampling period after injection and with premature ovulation. Analysis of data from hens injected centrally with doses of LHRH from 0.001 to 5.0 μg revealed a significant dose-response regression (P<0.01) with an ED50 of 0.53 μg. Five of six hens injected centrally with 5 μg LHRH responded with a premature ovulation, and all six treated birds showed increased plasma concentrations of LH, P4, and T within 30 min of the time of injection, compared with values obtained in vehicle-injected birds. We conclude that peripheral injections of unphysiologically high doses of T are capable of inducing premature ovulation, but that this effect is not mediated by T at the site of the hypothalamo-hypophyseal axis. In addition, LHRH injected i.v. or centrally 14–12 h prior to the first ovulation in a sequence is capable of inducing significant and sustained release of LH, P4, and T and premature ovulation.

Evidence that estradiol induces the preovulatory LH surge in cattle by increasing pituitary sensitivity to LHRH and then increasing LHRH release.

The objectives of these studies were to determine 1) the influence of estradiol on the ability of the pituitary gland to release LH in response to LHRH in vivo, and 2) whether LHRH is required to cause the preovulatory LH surge in cattle. To minimize the confounding effect of endogenous LHRH or LHRH-induced LH release, we used the estradiol-treated steer as a model for the cow. The rationale for this choice is that estradiol does not normally cause an LH surge in steers, but it does exert a negative feedback effect inhibiting LHRH secretion. In the first experiment, an LH surge was induced in steers by injecting 1 μg LHRH at 20-min intervals between 12 and 20 h after estradiol. This surge resembled the preovulatory LH surge in cows with respect to both duration (10 h) and amplitude (49 ng/ml). After the peak, LH concentrations returned to baseline despite continued LHRH injections. In control steers given oil, repetitive injections of LHRH increased serum LH to only 13 ng/ml. In a second experiment, steer...

The effect of short-term starvation on pituitary and plasma LH, plasma estradiol and progesterone, and on pituitary response to LH-RH in the laying hen ( Gallus domesticus)

The effect of starvation on pituitary and plasma LH, plasma estradiol and progesterone levels, and pituitary response to LH-RH in the laying hen were studied. Deprivation of food for 7 days prevented egg laying and significantly decreased plasma LH, estradiol, and progesterone concentrations, but did not significantly change pituitary LH concentration. Resumption of feeding raised plasma LH and progesterone to their initial levels, but increased plasma estradiol to a higher level than its initial level within 3–4 days of refeeding. A single injection of 20 μg LH-RH to intact laying hens before starvation significantly increased plasma LH. LH-RH at 20-μg dose failed to increase plasma LH on the third day of food withdrawal, but increased it to some extent on the seventh day. The hen recovered initial sensitivity to LH-RH in increasing plasma LH after 7 days of refeeding. These results indicate that starvation caused follicular atresia in the hen probably due to the decrease of gonadotrophin secretion from the pituitary, and that starvation may reduce pituitary gonadotrope sensitivity to LH-RH in the hen at least in the early stage of fasting.

Effects of RU16117, an orally active weak oestrogenic compound, in postmenopausal women

Daily oral administration of 1, 3 or 10 mg of RU16117 (11α-methoxy ethinyl oestradiol) to normal postmenopausal women led to a progressive decrease of basal serum LH levels to 60.4 ± 17.0, 35.1 ± 9.1 and 20.1 ± 2.8% of control (pretreatment values, P < 0.01), respectively, after 4 wk of drug administration. Although the pattern was similar, the inhibitory effect of RU16117 was even more pronounced on FSH than LH levels: a 50% decrease of basal LH and FSH levels was obtained at the daily 1.8 and 1.2 mg doses of RU16117, respectively. No significant change of basal serum gonadotrophin levels was observed with the daily 0.3 mg dose. Administration of 1 mg of RU16117 every second day or 10 mg once a week led to a relatively small but significant ( P < 0.05) 20–25% decrease of basal serum LH levels after 4 wk of treatment in four out of five women. While daily 0.3 and 1.0 mg doses of RU16117 had no significant effect on the LH response to 100 μg LHRH, the 3.0 mg dose delayed the response up to 90 min. The 10 mg dose, on the other hand, led to a markedly delayed and reduced response. Treatment for the same period (4 wk) with 1 mg RU16117 every second day or 10 mg once a week led to a small (20–25%, P < 0.05) inhibition of the LH response to LHRH. At the dose of 10 mg once a week, RU16117 had no or minimal effect on endometrial histology. Since RU16117, an orally active weak oestrogenic compound, has been shown to have anticarcinogenic activity in the rat, the present findings suggest that this new steroid could be useful for the treatment of climacteric symptoms.

Decreased pituitary responsiveness and inhibition of the luteinizing hormone surge and ovulation in the stumptailed monkey (Macaca arctoides) by chronic treatment with an agonist of luteinizing hormone-releasing hormone.

The purpose of this investigation was to determine if chronic treatment with D-Ser-(But)6-des-Gly10 LHRH ethylamide (LHRH agonist) could lead to an inhibitory effect on reproduction in the stumptailed macaque (Macaca arctoides). Nine adult monkeys, weighing 8–10.5 kg, with regular menstrual cycles of 29.7 ± 0.3 days (mean ± SEM) were selected. A single sc injection of 5 μg LHRH agonist stimulated LH secretion for 8 h; this was associated with an increased secretion of 17β-estradiol from the ovaries. Beginning on days 1-5 of the cycle, the monkeys were given daily sc injections of 5 fig LHRH agonist for 20 days. Blood samples were taken two or three times weekly (four monkeys) or daily (five monkeys) and assayed for progesterone, 17β-estradiol, and LH. Sampling was done 24 h after each injection of agonist and at regular intervals after the first and last injections. The normal rise in progesterone levels in the blood was prevented by agonist treatment in seven of the nine monkeys and in the remaining two ...

The hormonal status of patients with benign prostatic hypertrophy: FSH, LH, TSH and prolactin responses to releasing hormones.

SUMMARYIn order to determine whether the benign prostatic hypertrophy (BPH) adenoma is responsible for low serum LH levels in patients with this disease, we measured FSH, LH and prolactin in sera collected from patients before and 0.8–2.2 years after retro‐pubic prostatectomy, but found no change in their levels. Pituitary stimulation tests were therefore conducted to evaluate the pituitary hormone reserve in normal elderly men, and BPH patients before and after removal of the BPH adenoma. Blood was drawn 20 min before and during the administration of 100 μg LHRH and 200 μg TRH, as a single intravenous injection, and after 20, 60 and 120 min. Serum FSH, LH, TSH and prolactin were estimated by radioimmunoassays. Prior to prostatectomy, patients with BPH had significantly lower levels of serum LH, but not FSH, TSH or prolactin, as compared to normal men 20 min before the test. Serum LH in the BPH group after prostatectomy (1–2.75 years) was not statistically different from that of normal age‐matched men, but the mean level more closely resembled that of the untreated BPH group. Although there were no significant differences in serum levels of FSH or prolactin between subject groups during stimulation, levels of LH and TSH in untreated BPH patients' serum were significantly lower than those of normal men. The BPH patients after prostatectomy resembled the normal men under these circumstances, and the serum levels of TSH in these ex‐BPH patients were significantly higher than in untreated BPH patients. Similarly, the maximum LH and TSH responses to the hypothalamic releasing hormones were also significantly lower in the BPH patients as compared to normal age‐matched men, and evidently return to normal 1–2.75 years after prostatectomy. No statistically significant differences were observed in the FSH and prolactin responses to LHRH and TRH between groups. The results suggest that a factor originating from the BPH adenoma, such as 5α‐dihydrotestosterone, may be responsible for the suppression of pituitary LH and TSH responses to LHRH and TRH, respectively. It also appears that the pituitary of BPH patients does not regain its full secretory potential after the BPH adenoma has been removed, or that an additional factor may regulate pituitary LH secretion in the untreated and ex‐BPH patients at the hypothalamic level.