Doses Of Gonadotropin-releasing Hormone Research Articles

Effect of season on luteal activity during the post partum period of dairy cows in temperate areas

Seasonal effects on luteal activity during post partum were evaluated in two consecutive studies in 253 dairy cows in Northern Italy. In study 1, plasma progesterone concentrations were determined on days 14, 21, 28, 35, 42, 49 and 56 post partum and in study 2 cows were synchronized and inseminated at a fixed time using two regimes based on the ‘Ovsynch’ protocol. Study 1: Animals were classified as luteal (progesterone >1.5 ng/ml in at least two consecutive samples) or non-luteal (progesterone <1.5 ng/ml in all samples). The proportion of cows without luteal activity from calving to day 56 post partum was 47/253 (18.5%). Of the 47 cows without luteal activity, 42 (89%) were detected during the warm months of the year and five were detected during the cold months of the year, and the effect of season was highly significant (P < 0.001). Study 2: Three study groups were established; control (CONT, untreated cows, n = 92), GPG (cows receiving gonadotropin-releasing hormone (GnRH) on day 0, PGF2α on day 7 followed by a second dose of GnRH 24 h later, n = 80); and HPH (the same as the GPG group, but with human chorionic gonadotropin (hCG) substituted for GnRH, n = 81). In the GPG and HPH groups, cows were inseminated 16 to 22 h after the second GnRH or hCG injection. Untreated cows were inseminated at first estrus after a voluntary weaning period. Because the effects of the GPG and HPH regimes on pregnancy rate were not significantly different, data were pooled into a single treatment group (TREAT). Pregnancy rates during the warm months of the year were 16% and 15% at first service and 65% and 66% at day 135 post partum for CONT and TREAT groups, respectively. Pregnancy rates during the cold months of the year were 36% and 38% at first service and 72% and 76% at day 135 post partum for CONT and TREAT groups, respectively. There was an effect of season (P < 0.05) but not of treatment on pregnancy rate. Treatment reduced the number of days from calving to conception during both the cold (101 ± 3.2 v. 121 ± 3.1 days; P < 0.001) and warm seasons (122 ± 3.2 v. 145 ± 3.1 days; P < 0.001). In conclusion, the present study shows that (i) heat stress during the warm season can compromise luteal activity and (ii) that regimes based on the Ovsynch protocol did not improve pregnancy rate at first service or by 135 post partum, but they had a positive effect on the calving-to-conception interval.

Pituitary luteinizing hormone responses to single doses of exogenous GnRH in female social Cape ground squirrels exhibiting low reproductive skew

AbstractThe Cape ground squirrel Xerus inauris is unusual among social mammals as it exhibits a low reproductive skew, being a facultative plural breeder with not all females breeding within a group. We investigated pituitary function to assess whether there was reproductive inhibition at the level of the pituitary and potentially the hypothalamus in breeding and non‐breeding female Cape ground squirrels. We did so during the summer and winter periods by measuring luteinizing hormone (LH) responses to single doses of 2 g exogenous gonadotropin‐releasing hormone (GnRH) and physiological saline administered to 42 females from 11 colonies. Basal LH concentrations of females increased in response to the GnRH challenge. Basal plasma LH concentrations were greater during winter, when most oestrus events are observed. However, we found no differences in plasma LH concentrations between breeding and non‐breeding females. We showed that the anterior pituitary of non‐breeding female ground squirrels is no less sensitive to exogenously administered GnRH than that of breeding females. We therefore concluded that the pituitary is no more active in breeding than non‐breeding females. The lack of differentiation in response to GnRH suggests that either non‐breeding females have ovaries that are less sensitive to LH or that they refrain from sexual activity with males through an alternative mechanism of self‐restraint.

High-dose recombinant LH add-back strategy using high-dose GnRH antagonist is an innovative protocol compared with standard GnRH antagonist

High daily doses of gonadotrophin-releasing hormone (GnRH) antagonists during the follicular phase of ovarian stimulation were associated with low implantation rates. To test if this occurred because of profound pituitary suppression, the pituitary response was suppressed with a high-dose GnRH antagonist and recombinant LH (rLH) was added back to correct the implantation rate. An open-label, randomized, controlled, prospective clinical study in 60 patients undergoing IVF was performed. GnRH antagonist was initiated on day 6 of stimulation (2 mg/day) together with 375 IU rLH, and maintained until the day of HCG administration. Controls received 0.25 mg/day GnRH antagonist. Fluctuating LH concentrations were present on days 3 and 6 in both groups. This strong fluctuation continued on day 8 and on the day of HCG administration in the control (low-dose) group, where 30% of patients had LH concentrations <1 IU/l on the HCG day. The study (high-dose) group showed stable LH concentrations on day 8 and on the HCG day, with no LH surges. No clinical differences were found between groups. The LH add-back strategy (375 IU/day) rescued the adverse effects that high doses of GnRH imposed on implantation. These results suggest that rLH should be considered during ovarian stimulation with GnRH antagonist.

LH responses to single doses of exogenous GnRH in the Cape mole rat (Georychus capensis): the pituitary potential for opportunistic breeding

AbstractThe Cape mole rat Georychus capensis is a solitary mole rat that inhabits the winter rainfall region of the Western Cape Province of South Africa. Circulating basal concentrations of luteinizing hormone (LH) were found to be significantly higher in the breeding season in both sexes. During both the breeding and non‐breeding season, administration of exogenous gonadotropin‐releasing hormone (GnRH) increased circulatory LH levels. The magnitude of the LH response to an overdose of exogenous GnRH both in and out of the breeding season in males and females was not significantly different. Typically, seasonally breeding species exhibit a down‐regulation of the pituitary and reproductive functions out of the breeding season. It appears that there is no down‐regulation of GnRH receptors at the level of the pituitary out of the breeding season, because the pituitary responds to an exogenous GnRH challenge equally both in and out of the breeding period. The Cape mole rat exhibits the potential for opportunistic breeding out of the breeding period, provided that environmental factors are favourable. This finding questions whether this mole rat is actually a seasonal breeder or whether reproduction is hindered by the ecological constraint of the lack of opportunities to burrow and find mates at certain times of the year.

Dose-related actions of GnRH II analog in the cycling rhesus monkey

Introduction Gonadotropin-releasing hormone (GnRH) II expression, specific high-affinity receptors for GnRH II and its potent bioactivity in human and baboon tissues led us to hypothesize that GnRH II is a bioactive peptide in primates. We recently demonstrated the contraceptive activity of GnRH II analog in rhesus monkeys. In the present experiment, we extended those studies to the dose-related action of this analog on parameters of luteal function and conception. Methods GnRH II analog (0–32 μg/day) or saline was administered via osmotic minipumps for 6 days (Days 1–6 postovulation) to regularly cycling rhesus monkeys mated with fertile males around the time of ovulation. Cycle dynamics was monitored through circulating luteinizing hormone, progesterone and estradiol. Pregnancy was determined by circulating chorionic gonadotropin concentrations. Results Progesterone production (Days 3–11) was significantly less (p<.05) for animals treated with 2, 4 or 8 μg/mL GnRH II analog than for controls, yet with higher doses of GnRH II analog (i.e., 16 or 32 μg/day), luteal progesterone was not different from that of saline-treated controls. The length of the luteal phase in all treated groups was similar to that of controls. In 18 animals mated at the time of ovulation and then treated with GnRH II analog (2–32 μg/day), no pregnancies resulted. In saline-treated controls, five of eight animals (62.5%) became pregnant. Thus, the contraceptive activity of this GnRH II analog did not correlate with luteal progesterone inhibition. Conclusions These data demonstrate a dose-related action of GnRH II analog on luteal progesterone and establish the contraceptive activity of 2–32 μg/day GnRH II analog administered postovulation.

Graded inhibition of pulsatile luteinizing hormone secretion by a selective gonadotropin-releasing hormone (GnRH)-receptor antagonist in healthy men: evidence that age attenuates hypothalamic GnRH outflow.

Healthy older men manifest concomitant hypoandrogenemia and attenuation of LH pulse size. Because exogenous GnRH remains effective, a plausible intuition is that aging reduces hypothalamic GnRH secretion, thus mediating relative hypogonadotropic hypogonadism. To assess the impact of age on central GnRH outflow indirectly, we quantitated graded suppression of pulsatile LH secretion by saline and escalating doses of a potent and selective GnRH-receptor antagonist, ganirelix, in 18 healthy men ages 23-72 yr. The rationale is that ganirelix should reduce the amplitude of LH pulses in proportion to both drug concentration and endogenous GnRH feedforward. To this end, blood was sampled every 10 min for 2 h before and 16 h after sc administration of saline or ganirelix and for 3 additional hours after iv injection of a fixed dose of GnRH (100 ng/kg); concentrations of LH and ganirelix were measured by immunochemiluminometry and RIA, respectively; and pulsatile LH secretion was quantitated by a deconvolution procedure. Log-linear regression analysis was used to estimate the sensitivity of pulsatile LH secretion to inhibition by a unit increase in serum ganirelix concentrations in each subject. Statistical analyses revealed that increasing age markedly attenuated the capability of ganirelix to decrease LH pulse size (viz., r = -0.648; P = 0.004). In contrast, age did not modify the competitive interaction between injected GnRH and ganirelix. These joint outcomes support the clinical hypothesis that age diminishes hypothalamic GnRH outflow without impairing GnRH action in healthy men.

The Effect of Pretreatment with Different Doses of GnRH to Synchronize Follicular Wave on Superstimulation of Follicular Growth in Dairy Cattle

The objective of this study was to evaluate the efficiency of gonadotropin releasing hormone (GnRH) and GnRH doses in synchronizing follicular wave emergence as a pretreatment for superovulation in cattle. Fourteen Holstein-Friesian cows 6 days from estrus were randomly assigned to receive 100 microg (n=4), 50 microg (n=5), or 25 microg (n=5) of GnRH. Superovulation was induced with injections of porcine FSH (pFSH) twice daily, decreasing the dose (total 42 AU) over 5 days beginning 2.5 days after receiving GnRH. On the 7th and 8th injections of pFSH, 750 microg of PGF(2alpha) was also given. With the exception of one cow that was given 50 microg of GnRH, ovulation was induced in all cows from the three groups and the new follicular wave emergence was observed. The total number of follicles for the 25 microg GnRH group was less than that observed for the 100 microg GnRH group (P<0.05), although there were no differences between the 100 microg, 50 microg and 25 microg GnRH groups with respect to the number of preovulatory follicles (>or=10 mm) and CL. The numbers of normal embryos were greater for the 25 microg GnRH group than the 100 or 50 microg GnRH groups (P<0.01); however, the numbers of ova/embryos did not differ significantly between the three groups. These results suggest that 25 microg of GnRH was sufficient to induce ovulation and follicular wave emergence. On day 6 of the estrous cycle, a reduction of the dose of GnRH to synchronize follicular wave emergence as a pretreatment for superstimulation promotes transferable embryos.

A preclinical pharmacokinetic/pharmacodynamic approach to determine a dose of GnRH, for treatment of ovarian follicular cyst in cattle

The objective of this study was to explore the value of a preclinical PK/PD approach to determine a gonadotropin-releasing hormone (GnRH) dose in cows using the pituitary LH response as a surrogate endpoint. Using an indirect effect model with stimulation of the LH entry rate, the in vivo basic pharmacodynamic parameters of GnRH were determined. The EC(50) of GnRH was 51 +/- 16 pg/mL, the EC(50) being the GnRH plasma concentration able to produce 50% of the maximum possible stimulation (S(max)) of the hypophysis (S(max) = 48 +/- 13). From individual PK/PD parameters, the ED(50) of GnRH, i.e. the estimated dose of GnRH required to determine half the maximum possible stimulating effect on LH release, was calculated to 62 microg/h per cow. Using the PK/PD model, the GnRH dose required to achieve a selected breakpoint value of 5 ng/mL for maximum LH concentration (surrogate value for LH concentration predicting clinical efficacy for cystic conditions), was 52 +/- 18 microg and for a standard GnRH dose of 100 microg, the mean maximum plasma LH concentration predicted by the model was 7.22 +/- 0.98 ng/mL.

Involvement of Gonadotropin-Releasing Hormone in Thyroxine Release in Three different forms of Teleost Fish: Barfin Founder, Masu Salmon and Goldfish

Effects of gonadotropin-releasing hormone (GnRH) on thyroxine (T4) release in vivo and in vitro were studied in barfin flounder Verasper moseri, masu salmon Oncorhynchus masou and goldfish Carassius auratus. Seabream GnRH (sbGnRH) at a dose of 200 ng/50 g body weight (BW) significantly increased plasma T4 levels 1 h after the in vivo injection in the barfin flounder, but thereafter the levels normalized. Salmon GnRH (sGnRH) significantly increased plasma T4 levels l h after the injection with a significant return to initial levels in male masu salmon and male goldfish. In contrast, sGnRH and cGnRH-II in barfin flounder, and cGnRH-II in male masu salmon and male goldfish were not effective in stimulating T4 release. To clarify direct involvement of GnRH in T4 release, dissected lower jaw including scattered thyroid follicles was incubated with sbGnRH (1 µg/well) in barfin flounder, and with two doses (0.1 and 1 µg/well) of sGnRH in masu salmon and goldfish in vitro. T4 concentrations of control were stable during 24 h. Incubation of lower jaw with high dose (1 µg/well) of GnRH significantly (P<0.05) increased T4 concentrations of incubation medium at 1 h in all experimental fishes. These results indicate that direct stimulation of T4 secretion by GnRH occurs widely in teleost fish.

Strategic use of gonadotrophin-releasing hormone (GnRH) to increase pregnancy rate and reduce pregnancy loss in lactating dairy cows subjected to synchronization of ovulation and timed insemination

The objective of this study was to determine the effect of GnRH (100 μg i.m.) treatment 5 and 15 days after timed insemination (TAI) on pregnancy rate and pregnancy loss in lactating dairy cows subjected to synchronization of ovulation. The study included 831 lactating dairy cows subjected to a Presynch–Ovsynch protocol for first service. On the day of TAI (Day 0), cows were randomly assigned to one of four experimental groups. Cows in Group 1 ( n = 214) were treated with GnRH on Day 5; cows in Group 2 ( n = 209) were treated with GnRH on Day 15; cows in Group 3 ( n = 212) were treated with GnRH on both Day 5 and Day 15; cows in Group 4 ( n = 196) were not treated. Pregnancy rate was evaluated at Day 27 and Day 45 after TAI. The interestrus interval and the proportion of cows diagnosed not pregnant based on expression of estrus and insemination before pregnancy diagnosis on Day 27 were determined. The results of this study are: (1) GnRH treatment on Day 5 or Day 15 did not increase pregnancy rate, or reduce pregnancy loss between Day 27 and Day 55 after TAI; (2) cows treated with GnRH on both Day 5 and Day 15 had a lower ( P < 0.01) proportion of cows diagnosed not pregnant based on expression of estrus before ultrasonography on Day 27 (26.5%) compared to control cows (52.9%), and these cows had an extended ( P = 0.05) interestrus interval (23.4 days vs. 21.5 days); and (3) GnRH treatment on both Day 5 and Day 15 after TAI reduced pregnancy rate on Day 27 (36.8% vs. 44.4% for control cows; P < 0.03) and Day 55 (28.3% vs. 36.2% for control cows; P < 0.01). Therefore, strategies to stimulate CL function using multiple doses of GnRH during the luteal phase need to consider potential negative effects.

Comparison of two different starting multiple dose gonadotropin-releasing hormone antagonist protocols in a selected group of in vitro fertilization–embryo transfer patients

Objective To compare the efficacy of two starting protocols of multiple dose GnRH antagonists (GnRH-a). Design Prospective randomized controlled study. Setting In vitro fertilization–embryo transfer program at the Instituto Valenciano de Infertilidad, Valencia, Spain. Patient(s) One hundred nine patients undergoing controlled ovarian hyperstimulation (COH) with recombinant gonadotropins and GnRH-a (0.25 mg/d). Intervention(s) Patients started GnRH-a administration on stimulation day 6 (group 1) or when the leading follicle reached a mean diameter of 14 mm (group 2). Main outcome measure(s) Implantation and pregnancy rates; serum E 2 and LH levels during ovarian stimulation; days of stimulation and GnRH-a administration. Result(s) Days needed for ovarian stimulation were similar in both groups but there was a significant difference when comparing days of GnRH-a administration. Serum E 2 and LH followed similar curves in both groups. Implantation and pregnancy rates were 23.7% and 44.4 % in group 1 and 28.6% and 50.9 % in group 2 ( P=not significant [NS]). Conclusion(s) The efficacy of the two starting protocols of the multiple dose GnRH-a evaluated in this study is similar; however, this remark can only be drawn for a selected group of patients.

Low dose gonadotropin-releasing hormone agonist treatments with early discontinuation for controlled ovarian hyperstimulation in an in vitro fertilization program.

Aim: The purpose of the present study was to investigate the applicability of a protocol for controlled ovarian hyperstimulation (COH) featuring early discontinuation of low dose gonadotropin-releasing hormone agonist (GnRHa) for ovulation induction for in vitro fertilization (IVF). Methods: Four hundred and eighty-seven women undergoing 555 IVF cycles were recruited into the study. Controlled ovarian hyperstimulation was achieved by using either a short protocol of low dose GnRHa (for 5days only; groups 1 and 2) or a modified long protocol with early discontinuation of GnRHa (groups 3 and 4). Groups 1 and 3 received urinary follicle-stimulating hormone (FSH) and groups 2 and 4 received recombinant FSH. Oocyte retrieval was performed 34 to 36h after human chorionic gonadotropin (hCG) injection, followed by embryo transfer 3days later. Results: Luteinizing hormone (LH) levels on the hCG injection day were lower with the modified long protocol (groups 3 and 4) than with the short 5-day treatment (groups 1 and 2). There were higher LH levels in group 1 than in groups 2, 3 and 4, resulting in a worse fertilization rate and clinical pregnancy rate. There were no statistically significant differences between groups 2, 3 and 4 in the rates of fertilization, clinical pregnancy and delivery. A higher estradiol (E2) level in group 3 than in groups 1, 2 and 4 resulted in a worse implantation rate. Conclusion: Early cessation of GnRHa may not induce a premature LH surge in controlled ovarian hyperstimulation, while a low dose also offers a useful alternative to a long protocol of IVF. Ovarian stimulation with recombinant follicle-stimulating hormone (rFSH) is considered to be favorable in this low dose GnRHa treatment. (Reprod Med Biol 2003; 2: 25-30).

Single dose gonadotropin releasing hormone (GnRH) antagonist cetrotide tm is effective in luteinizing hormone (LH) surge suppression for in vitro fertilization (IVF)

Single dose gonadotropin releasing hormone (GnRH) antagonist cetrotide tm is effective in luteinizing hormone (LH) surge suppression for in vitro fertilization (IVF)

Recovery of Spermatogenesis by High Dose Gonadotropin-Releasing Hormone Analogue Treatment in Rat Cryptorchid Testis after Orchiopexy

Cryptorchidism is an adverse condition of spermatogenesis in many mammals. Surgical cryptorchidism in rats lasting more than a few weeks is so detrimental that spermatogenesis cannot be completely recovered even after orchiopexy. We evaluated the efficacy of the high dose gonadotropin-releasing hormone (Gn-RH) agonist leuprorelin acetate on damaged spermatogenesis in rat cryptorchid testes. Male Fisher rats were divided into 2 groups of 6 each and bilateral cryptorchidism was artificially produced. Five weeks later all rats underwent bilateral orchiopexy. One group served as the control, while the other received Gn-RH agonist injections at orchiopexy and 4 weeks later. The animals were sacrificed 15 weeks after orchiopexy. The weight of the body, testis and epididymis was measured and the histology of spermatogenesis was examined. For statistical analysis the Student t test was applied. Testes in the Gn-RH group rats showed significant recovery of spermatogenesis up to complete spermatozoa formation, while those in control rats remained almost degenerated. The mean incidence of seminiferous tubules with recovered spermatogenesis plus or minus standard deviation was significantly higher in the Gn-RH than in the control group (87.8% +/- 6.0% versus 12.5% +/- 7.7%, p <0.001). Administering the high dose Gn-RH agonist leuprorelin acetate after orchiopexy greatly enhanced the recovery of spermatogenesis in rats. This finding is in accordance with other recent reports that treatment with Gn-RH analogues promotes the regeneration of once damaged spermatogenesis. On the other hand, these findings may cause one to question supplementation therapy now used in regular practice to boys with cryptorchidism.

Recovery of Spermatogenesis by High Dose Gonadotropin-Releasing Hormone Analogue Treatment in Rat Cryptorchid Testis after Orchiopexy

Recovery of Spermatogenesis by High Dose Gonadotropin-Releasing Hormone Analogue Treatment in Rat Cryptorchid Testis after Orchiopexy

Effects of Soy Consumption on Gonadotropin Secretion and Acute Pituitary Responses to Gonadotropin-Releasing Hormone in Women

Soy contains the isoflavone phytoestrogens, genistein and daidzein. These isoflavones are partial estrogen agonists in cell and animal models, but effects from dietary soy in humans are unclear. Experiments were conducted in pre- and postmenopausal women to examine whether dietary isoflavones from soy behave as estrogen agonists, antagonists or have no effect on the estrogen-sensitive pituitary. Pituitary sensitivity to gonadotropin-releasing hormone (GnRH), an estrogen-sensitive endpoint, was measured during GnRH challenge tests administered before, during and after dietary soy consumption. The response to an isoflavone-rich soy food diet was examined in five premenopausal and seven postmenopausal women using transdermal estrogen replacement therapy. Estrogen agonists suppress gonadotropin concentrations and enhance GnRH priming (enhanced gonadotropin secretion in response to repeated doses of GnRH), whereas antagonists elevate gonadotropin concentrations and have no effect on GnRH priming. Each subject consumed 50 g textured soy protein containing 60 mg total isoflavones daily for 10-14 d. Baseline estradiol concentrations were consistent among study periods. In both pre- and postmenopausal women, soy consumption did not affect mean baseline or peak luteinizing hormone (LH) concentrations, indicating a lack of estrogen-like effect at the level of the pituitary. However, in postmenopausal subjects, mean LH secretion decreased after discontinuing soy, suggesting a residual estrogenic effect. In one premenopausal woman, enhanced LH secretion was observed after soy treatment, suggesting there may be subpopulations of women who are highly sensitive to isoflavones.

Ovarian hyperstimulation-like syndrome after administration of triptorelin to a woman with endometriosis

Ovarian hyperstimulation after a single dose of gonadotropin-releasing hormone (GnRH) analog is a rare phenomenon. A case of ovarian hyperstimulation-like syndrome after sole administration of triptorelin(Decapeptyl 3.75 mg) is reported in a woman who had undergone surgery for an endometriotic cyst. After administration of the drug, abdominal pressure increased with nausea and diffuse pelvic pain. Ultrasoundexamination showed bilateral enlargement of the ovaries (right 74 × 62 mm, left 62 × 53 mm), more than 10 follicles ranging in diameter from 15-25 mm, proliferative endometrium 7 mm thick andfluid in the Douglas pouch up to 25 × 23 mm thick. Estradiol plasma level was in the normal range. The syndrome spontaneously resolved in the course of treatment and a spontaneous pregnancy occurredwhen the triptorelin effect disappeared.

Progress towards the development of non-peptide orally-active gonadotropin-releasing hormone (GnRH) antagonists: therapeutic implications.

Gonadotropin-releasing hormone (GnRH) is a decapeptide (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly.NH2) which is produced from a precursor polypeptide in hypothalamic neurons and secreted in a pulsatile fashion to stimulate the secretion of LH and FSH via its interaction with a cognate receptor on gonadotropes. Low doses of the native peptide delivered in a pulsatile manner to mimic that found in the hypothalamic portal vessels restore fertility in hypogonadal patients, and are also effective in treating cryptorchidism and delayed puberty. Administration of high doses of GnRH, or agonist analogues, causes desensitization of the gonadotrope with consequent decline in gonadal gametogenesis and steroid and peptide hormone synthesis. This phenomenon finds extensive therapeutic application in clinical medicine in a wide spectrum of disease (Table 1). In addition, GnRH analogues have promise as new generation male and female contraceptives in conjunction with steroid hormone replacement. GnRH antagonists inhibit the reproductive system through competition with endogenous GnRH for the receptor and, in view of their rapid effects, are being increasingly used for the above mentioned applications. The peptide agonists and antagonists currently available require parenteral administration, typically in the form of long-acting depots. A new generation of non-peptide GnRH antagonists are beginning to emerge which should allow oral administration and, therefore, may provide greater flexibility of dosing, lower costs and increased patient acceptance.

Development of a gonadotrophin-releasing hormone and prostaglandin regimen for the planned breeding of dairy cows

Four studies were carried out to determine the ovarian responses of dairy cows undergoing natural oestrous cycles to sequential injections of gonadotrophin-releasing hormone (GnRH), followed seven days later by prostaglandin...

Influence of dose, frequency, and duration of infused gonadotropin-releasing hormone on secretion of luteinizing hormone and follicle-stimulating hormone in nutritionally anestrous beef cows

Nutritionally induced anovulatory cows were ovariectomized and used to determine the relationships between dose, frequency, and duration of exogenous gonadotropin-releasing hormone (GnRH) pulses and amplitude, frequency, and concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in serum. In Experiment 1, cows were given pulses of saline (control) or 2 μg of GnRH infused iv during a 0.1-, 1.25-, 5-, 10-, or 20-min period. Concentrations of LH and FSH during 35 min after GnRH infusion were greater than in control cows (P < 0.01), and FSH concentrations were greater when GnRH infusions were for 10 min or less compared with 20 min. In Experiment 2, the effect of GnRH pulse frequency and dose on LH and FSH concentrations, pulse frequency, and pulse amplitude were determined. Exogenous GnRH (0, 2, or 4 μg) was infused in 5 min at frequencies of once every hour or once every 4th hr for 3 d. There was a dose of GnRH × frequency × day effect on LH and FSH concentrations (P < 0.01), indicating that gonadotropes are sensitive to changes in pulse frequency, dose, and time of exposure to GnRH. There were more LH pulses when GnRH was infused every hour, compared with an infusion every 4th hr (P < 0.04). Amplitudes of LH pulses were greater with increased GnRH dose (P < 0.05), and there was a frequency × dose × day effect on FSH pulse amplitude (P < 0.0006). We conclude that LH and FSH secretion in the bovine is differentially regulated by frequency and dose of GnRH infusions.