FSH and LH plasma levels in bitches with differences in risk for urinary incontinence

To determine whether the height of the plasma gonadotropin levels after spaying is associated with urinary incontinence, the concentrations of plasma follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined once in 191 intact and 308 spayed bitches. The bitches were grouped according to their risk for urinary incontinence and the medians of their respective gonadotropin levels were compared. For intact anestrous bitches, the FSH- and LH-plasma concentrations were 5.2 (4, 8) ng/mL (median (Q1, Q3)) and 0.5 (0.5-0.5) ng/mL, respectively. In the first year after spaying, the gonadotropin concentrations rose significantly, then stabilised at a level around 10 times those of intact bitches (FSH 62.5 (44, 91) ng/mL; LH 6.1(4, 11) ng/mL). The plasma gonadotropin concentrations of long-term spayed (>12 months) continent bitches (n=209) were higher (FSH 66.8 (46, 104) ng/mL; LH 6.5 (4, 11) ng/mL) than in spayed incontinent bitches (n=60) (FSH 51.5 (38, 74) ng/mL; LH 5.5 (3, 8) ng/mL), the latter also had a higher body weight. Multiple regression analysis showed that the FSH-plasma concentration and not the body weight was decisive for the occurrence of urinary incontinence. The results of this study suggest that levels of gonadotropins are associated, directly or indirectly in the pathophysiology of urinary incontinence after spaying.     

Effect of a long acting GnRH analogue or placebo on plasma LH/FSH, urethral pressure profiles and clinical signs of urinary incontinence due to Sphincter mechanism incompetence in bitches

In 23 bitches with urinary incontinence due to spaying, the effect of treatment with a long-acting formulation of leuprolide acetate on frequency of incontinence, plasma gonadotropin levels and urodynamic parameters was evaluated. In addition, the clinical effect was compared with that of treatment with alpha-adrenergics. Before treatment, the dogs' incontinent episodes occurred, on average, 4 times per day on up to 6 days per week. In the pre-trial after therapy with phenylpropanolamine (n=23) the episodes of incontinence decreased by 92%, in the double-blind study 5 weeks after GnRH-analogue (n=11) by 71%; and by 28% after the placebo (n=12). By the end of the study, nine of twenty-two leuprolide treated bitches responded completely to treatment and were continent for periods lasting 70-575 days after treatment. In another 10 dogs, response to therapy was partial and the frequency of incontinence was reduced by at least 50%. After therapy with placebo, one bitch had no episodes of incontinence for 412 days. Treatment with the GnRH-analogue significantly decreased the plasma gonadotropin levels but there was no correlation between the effect on gonadotropin levels and response to treatment. Treatment with leuprolide or placebo had no effect on urethral closure pressure regardless of the response to treatment. The hypothesis that the change of the plasma gonadotropin levels after spaying is the cause of reduced urethral closure function was not supported by the results of this study. A possible direct effect of GnRH-analogues on the bladder is discussed. Long acting GnRH analogues appear to be a well-tolerated alternative for urinary incontinence treatment, but they appear to be less effective than the alpha-adrenergics.     

Pulsatile plasma profiles of FSH and LH before and during medroxyprogesterone acetate treatment in the bitch

The aim of this study was to investigate the effect of medroxyprogesterone acetate (MPA) on pulsatile secretion of gonadotropins in the bitch. Five intact Beagle bitches were treated with MPA in a dose of 10mg/kg body weight subcutaneously at intervals of 4 weeks for a total of 13 injections, starting during anestrus. The 6-h plasma profiles of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were determined before, and 3, 6, 9, and 12 months after the start of MPA treatment. After 6 months of MPA treatment basal plasma LH concentration was transiently increased significantly. Basal plasma FSH concentration and the area under the curve above the zero level (AUC0) for FSH were significantly higher after 3 months of MPA treatment than before or after 9 and 12 months of treatment. MPA treatment did not significantly affect pulse frequency, pulse amplitude, or AUC above the baseline for either LH or FSH. During treatment 58 significant LH pulses were identified, and although each LH pulse coincided with an increase in plasma FSH concentration, in 17 cases the amplitude of the increase was too small to be recognized as a significant FSH pulse. In conclusion, MPA treatment did not suppress basal plasma gonadotropin levels in the bitches. On the contrary, it caused a temporary rise in the basal concentration of both FSH and LH, which may have been due to a direct effect of MPA on the ovary. In addition, several LH pulses were not accompanied by a significant FSH pulse, suggesting that MPA treatment attenuated the pulsatile pituitary release of FSH.     

Effects of continuous LHRH infusion on plasma levels of LH and FSH in males, before and after oestrogen or anti-oestrogen treatment

In order to study the role of oestrogens on gonadotrophin release in the human male, LHRH was administered as an infusion at a constant rate of 0.5 micrograms/minute for 4 hours to 7 normogonadotrophic oligozoospermic men, 6 eugonadal male-to-female transsexuals and 9 eugonadal male volunteers. In agreement with in vitro data a biphasic release pattern of both LH and FSH was observed in eugonadal transsexuals as well as in normogonadotrophic oligozoospermic men. In the latter the release of LH was greater than in eugonadal transsexual males and volunteers, which points to a different functioning of the hypothalamic-pituitary unit in normogonadotrophic oligozoospermic men. On the other hand the FSH response to LHRH stimulation was normal in these men. Three months' treatment with the oestrogen-receptor antagonist tamoxifen (TAM) (10 mg twice daily) in the normogonadotrophic oligozoospermic men stimulated basal LH, FSH and testosterone (T) levels. The fact that gonadotrophin levels rose in spite of increased T levels, suggests a role of endogenous oestrogens in the negative feedback regulation of gonadotrophin release in these men. Upon TAM treatment the first phase, the plateau and the second phase of LH release were augmented, whereas only the plateau and the second phase of FSH release were increased. Six weeks' administration of the oestrogen ethinyloestradiol (EE) (10 micrograms three times a day) in the eugonadal transsexual males suppressed basal T and oestradiol (E2) levels without affecting basal gonadotrophin levels significantly. In EE-treated males the first phase of LH release tended to be lower, whereas the plateau of LH had decreased significantly. The second phase of LH was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Basal and GnRH-induced secretion of FSH and LH in anestrous versus ovariectomized bitches

The basal and gonadotropin releasing hormone (GnRH)-induced plasma concentrations of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were studied in four anestrous and four ovariectomized (OVX) bitches. Blood samples were obtained via jugular venipuncture 40min before and 0, 10, 20, 30, 60, 90, and 120min after the i.v. administration of synthetic GnRH in a dose of 10microg/kg body weight. The basal plasma FSH and LH concentrations were significantly higher in the OVX bitches than in the anestrous bitches. In the anestrous bitches, the plasma FSH concentration was significantly higher than the pretreatment level at 10, 20, and 30min, whereas the plasma LH concentration was significantly elevated at 10 and 20min. The maximal GnRH-induced plasma FSH concentration in the anestrous bitches did not surpass the lowest plasma FSH concentration in the OVX bitches, whereas the GnRH-induced plasma LH concentrations in the anestrous bitches overlapped with the basal plasma LH concentrations in the OVX bitches. In the OVX bitches, GnRH administration did not induce a significant change in the plasma FSH concentration, whereas the plasma LH concentration increased significantly at 10 and 20min. In conclusion, the results of the present study indicate that in anestrous bitches GnRH challenge results in increased plasma levels of both FSH and LH, whereas in the OVX bitches, in which the basal plasma FSH and LH concentrations are higher, only a rise in the plasma LH concentration is present after GnRH stimulation. The results also suggest that a test to measure plasma concentration of FSH in single samples appears to have potential in verification of neuter status in bitches.     

Comparisons of estradiol,LH and FSH patterns in pregnant and nonpregnant beagle bitches

To characterize plasma estradiol, LH and FSH patterns of secretion during the bitch estrous cycle, blood samples were obtained daily from 15 days before until 135 days after the LH surge in 10 pregnant and 10 nonpregnant beagle bitches. After an initial increase between days 15 and 10 and an expected proestrous peak, estradiol concentrations increased again from days 9-12 (corresponding to cytological metestrus) from basal values observed around day 9 after the LH surge, and remained significantly elevated throughout the luteal phase both in pregnant and nonpregnant animals. Concomitantly with the end of the luteal phase, plasma concentrations of estradiol returned to basal values in both groups. During the mid- to late-luteal phase, mean basal LH secretion was significantly elevated throughout in the pregnant relative to the nonpregnant animals. However, in nonpregnant animals, pulsatility was increased and peaks of higher amplitude were observed. The plasma FSH profiles, determined by a specific homologous RIA, differed significantly between pregnant and nonpregnant bitches during the last two-thirds of the luteal phase with a mean FSH level more elevated during pregnancy. The FSH level then decreased around parturition and low concentrations during lactation period were observed. The FSH concentrations remained steady in nonpregnant luteal phases from early luteal phase through mid-anestrus. The differences in pregnant and nonpregnant LH and FSH concentrations suggest pregnancy differences in regulation of the corpus luteum. Finally, the elevated estradiol concentrations observed during the luteal phase of both pregnant and nonpregnant animals suggest that an ovarian production of estrogens may be involved in overall corpus luteum regulation in dogs as in other species.     

Effects of treatment with LH and FSH between 8 and 12 weeks of age on ovarian follicular development and puberty in heifers

The transient increase in gonadotrophin secretion, seen in heifer calves between 6 and 20 wk of age, may be critical for early ovarian follicular growth and for initiation of sexual maturation. We treated heifers with either 3 mg of bLH (n = 5; sc) or 4 mg sc of bFSH (n = 5; sc), every other day, between 8 and 12 wk of age. During the first 17 d of treatment, bovine gonadotrophins caused a reduction in maximum antral follicle size and in numbers of large antral follicles, compared to control heifers (P < 0.05). In 4 of 5 bLH treated heifers and 3 of 5 bFSH treated heifers, the emergence of a large dominant antral follicle was delayed (P < 0.05). At 34 wk of age, follicular dynamics did not differ among groups. Serum concentrations of estradiol were decreased in bFSH and bLH treated heifers at 35 wk of age and in bFSH treated heifers at 25 wk of age compared with that of the controls. Time of first ovulation was delayed in bFSH treated heifers compared with control heifers (P < 0.05;bFSH 59.0 +/- 1.2; control 51.4 +/- 1.8; bLH 56.2 +/- 2.5 wk of age). In summary, treatment of 8-wk old heifers with gonadotrophins every other day disrupted folliculogenesis over a 17-d period, delayed first ovulation (bFSH), and decreased ovarian estradiol production at 25 (bFSH) and 35 (bLH, bFSH) weeks of age.     

Effects of treatment with LH or FSH from 4 to 8 weeks of age on the attainment of puberty in bull calves

A transient increase in gonadotropin secretion between 6 and 20 weeks of age is critical for the onset of puberty in bull calves. To try and hasten the onset of puberty, bull calves were treated (s.c.) with 3 mg of bLH (n = 6) or 4 mg of bFSH (n = 6) once every 2 days, from 4 to 8 weeks after birth; control calves received saline (n = 6). At 4 and 8 weeks of age, mean LH concentrations were higher (P < 0.05) in bLH-treated (2.3 +/- 0.04 ng/ml and 1.20 +/- 0.04 ng/ml) as compared to control calves (0.50 +/- 0.1 ng/ml and 0.70 +/- 0.10 ng/ml). Mean serum FSH concentrations at 4 and 8 weeks of age, were higher (P < 0.05) in bFSH-treated (1.60 +/- 0.20 ng/ml and 1.10 +/- 0.2 ng/ml) as compared to control calves (0.38 +/- 0.07 ng/ml and 0.35 +/- 0.07 ng/ml). The age at which scrotal circumference (SC) first reached > or = 28 cm, occurred earlier (P < 0.05) in bFSH-treated calves as compared to saline-treated calves (39.3 +/- 1.3 and 44.8 +/- 1.3 weeks of age, respectively). Based on testicular histology at 56 weeks of age, treatment with bFSH resulted in greater (P < 0.05) numbers of Sertoli cells (5 +/- 0.2, 6 +/- 0.3 and 5 +/- 0.3 in bLH-, bFSH- and saline-treated calves, respectively); elongated spermatids (42 +/- 2, 57 +/- 8 and 38 +/- 5 in bLH-, bFSH- and saline-treated calves, respectively) and spermatocytes (31 +/- 3, 38 +/- 3 and 29 +/- 2 in bLH-, bFSH- and saline-treated calves, respectively) per seminiferous tubule. We concluded that treatment of bull calves with bFSH from 4 to 8 weeks of age increased testicular growth (SC); hastened onset of puberty (SC > or = 28 cm); and enhanced spermatogenesis.     

Effects of naloxone infusion on plasma levels of LH, FSH, and in addition TSH and prolactin in males, before and after oestrogen or anti-oestrogen treatment

The inhibitory action of endogenous opioids on gonadotrophin release is now well documented. Since LHRH-producing neurons do not possess oestrogen-receptors, it is likely that some other compound mediates the negative feedback action of oestrogens on the gonadotrophin release in the male. To test the hypothesis that endogenous opioids are implicated in this negative feedback action in the human male, the opioid receptor antagonist naloxone (2 mg/h for 4 h) was infused into 7 normogonadotrophic oligozoospermic men before and after 6 weeks of treatment with the oestrogen-receptor antagonist tamoxifen (TAM) (10 mg twice daily) and 6 eugonadal transsexual males before and after 6 weeks of administration of ethinyloestradiol (EE) (10 micrograms three times a day). The effects of naloxone on TSH and prolactin (PRL) release were also studied. Naloxone administration resulted in a significant release of gonadotrophins, but not of TSH and PRL. Administration of oestrogen and anti-oestrogen did not significantly affect the response of gonadotrophins to naloxone infusion and no evidence of consistently antagonistic effects of oestrogen and anti-oestrogen on the naloxone-induced gonadotrophin release was obtained. This shows that endogenous opioids are probably not intermediary in the negative feedback control of oestrogens on gonadotrophin release in the human male. Surprisingly, in contrast to the eugonadal transsexual males, FSH levels in the oligozoospermic men did not respond to naloxone administration. As naloxone is thought to exert its action on gonadotrophin release via a disinhibition of endogenous LHRH release, this finding is unexpected. Exogenous LHRH administration leads to a normal response of FSH in normogonadotrophic oligozoospermic men. No plausible explanation for this finding can presently be offered.     

Release of lutropin (LH) and follitropin (FSH) in cattle after administration of a new gonadoliberin (GnRH) analogue in comparison with the gonadoliberin decapeptide.

A gonadoliberin (GnRH) analogue nonapeptide (Hoe 766) was administered intramuscularly in concentrations between 2.5 and 50 μg to m?ture cows in order to study the response of lutropin (LH) and follitropin (FSH). Results were compared with those from experiments of the GnRH decapeptide (Hoe 471). Plasma LH and FSH were radio-immunologically determined. Increasing doses of GnRH analogue up to 15–20 μg caused an approximately linear increase in total plasma LH and FSH until the response reached a plateau. With these amounts peak values were about 60 fold higher for LH and 3.5 fold higher for FSH than basal levels about 135 minutes after injection. Higher values lasted for more than 6 h for LH and about 5 h for FSH. The LH response was much greater and more prolonged than for FSH.Doses of the nonapeptide analogue 50 to 70 times lower than the GnRH decapeptide provoked about the same height and duration of LH and FSH response.     

Effects of pentobarbital on serum levels of LH and FSH, in normal conditions and after GnRH stimulation: preliminary report

The authors have tested serum levels of LH and FSH in healthy males anaesthetized with 20 mg/Kg body weight of pentobarbital, and stimulation test with GnRH. LH has reached levels higher than the stimulation test has been practised in the anaesthetized volunteers than in subjects awakes. The AA. have also showed that there is no effect on psychic stress and of atropine, used as preanaesthetic drug, on serum levels of the pituitary hormones. At the end, PB has no effect on serum levels of FSH.     

Circadian variations in plasma LH and FSH in juvenile and adult male mice

Experiments were performed to ascertain circadian fluctuations in plasma levels of LH and FSH in juvenile and adult male mice. Animals under natural lighting (11 h day/13 h night) were killed at 1-hour intervals over a 24-hour period. There were large variations in plasma LH concentrations between animals sacrificed within each killing period. Baseline LH levels (values lower than 60 ng/ml) showed a significant 24-hour periodicity in adult males. FSH concentrations exhibited significant diurnal variations in juvenile and adult males. There was significant influence of age on the temporal pattern and 24-hour mean plasma hormone levels.     

Differential actions of GnRH and rat hypothalamic extracts in release of hypophysial FSH and LH in vitro.

A study was made of the separate patterns of luteinizing hormone (LH) and follicle stimulating hormone (FSH) release from isolated rat pituitary tissue evoked by synthetic gonadotropin releasing hormone (GnRH) or female hypothalamic extracts (HE), respectively, in a continuous perifusion system. Under defined conditions, gonadotropin release from hemipituitaries was relatively stable and reproducible. Absolute levels of LH and FSH release evoked by HE in terms of their GnRH content were always greater than those following exposure to synthetic GnRH at varying doses. Synthetic GnRH released more FSH than LH. In contrast, the HE released slightly higher levels of LH than FSH. The data suggest that the female rat hypothalamus contains substances other than GnRH, capable of releasing both LH and FSH. It is possible that such unidentified components can modify the hypophysial action of GnRH, resulting in particular circumstances in a differential release of LH and FSH.     

Oestradiol-17beta responsiveness, plasma LH profiles, pituitary LH and FSH concentrations in long-term ovariectomised Holstein cows at 24 h, 48 h and 21 days following treatment with an absorbable GnRH agonist implant

Non-lactating OVX Holstein cows (N = 34) were used to investigate the effect of s.c. placement of an absorbable GnRH agonist implant (Ovuplant; deslorelin 2.1mg, Peptech Animal Health, Australia) on the relationship of plasma LH, oestradiol responsiveness and pituitary LH content. On the day of implant insertion (Day 0), one group (OVU-48h; N = 5) received Ovuplant and had blood samples collected at hourly intervals to characterize the LH response, while a second group (CON-48 h; N = 5) remained untreated and acted as controls. Blood samples were collected every 10 min over 6 h from CON-48 h and OVU-48 h, at 24 h post-implant insertion. These cows were then slaughtered at 48 h post-implant insertion and their pituitaries recovered. Another group received Ovuplant (OVU-21d+E2; N = 10) or were left untreated (CON-21d+E2) and 21 days later were injected i.m. with 0.5 mg 17beta-E2. Blood samples were collected every 10 min for 4 h on the day before E2 injection to characterize LH pulse frequency and amplitude. Beginning 14 h later, blood samples were collected hourly for 12 h to characterize the expected LH surge. These cows were slaughtered and their pituitary glands recovered and assayed for LH and FSH content. Peak plasma LH concentrations (59 +/- 19 ng/ml) were measured after 30 min of Ovuplant insertion. They had returned to pre-treatment levels by 7 h. By 24 h post-implant insertion, OVU-48 h plasma LH profiles were characterized by reduced LH pulse frequency (0.23 +/- 0.09 pulses/h versus 0.75 +/- 0.26 pulses/h; OVU-48 h versus CON-48 h; P < 0.05). The cows that received Ovuplant had lower LH pulse amplitude, LH pulse frequency and mean LH concentrations after 20 days. Injection of 0.5 mg 17beta-E2 induced an LH surge in every one of the control cows with their peak concentrations measured 18 h post injection. No increase in LH was detected in any Ovuplant treated cows. Pituitary FSH content was reduced in Ovuplant treated cows after 48 h, but not that of LH. In conclusion, absorbable deslorelin implants induced a substantial but temporary release of LH, but even 21 days later their LH profiles were characterized by marked suppression of pulsatile LH and an absence of response to E2. These results suggest the implant has prolonged biological activity.     

Timing of multiple ovulations in the ewe after treatment with FSH or PMSG with and without GnRH

Ovulation rate, median time to first ovulation, median time of all ovulations and median time from first to last ovulation were studied by repeated laparoscopy in Merino ewes. Treatments with FSH or PMSG significantly affected ovulation rate (8.4 +/- 0.81 and 7.3 +/- 1.21 respectively, P less than 0.05) and in median time of all ovulations (60 and 54 h respectively after progestagen sponge removal, P less than 0.05). Differences in the median time to first ovulation (60 and 48 h) and median time from first to last ovulation (6 and 6 h) for the respective treatments were not significant. The synchrony of ovulation after both treatments was adversely affected by (1) the occurrence of premature ovulations before the onset of superovulation, (2) variability in the time of commencement of superovulation, and (3) variability in the time from first to last ovulation. Administration of GnRH synchronized the timing of ovulation with both gonadotrophin treatments. This synchrony was due to a reduction in the period during which superovulation began and in the interval from first to last ovulation. The median time of all ovulations was significantly less with FSH + GnRH than with PMSG + GnRH (45 and 48 h after progestagen sponge removal, respectively, P less than 0.05). Administration of GnRH at 16, 20 or 24 h after progestagen sponge removal significantly affected all traits examined except ovulation rate. Administration at 20 and 24 h produced an equally good synchrony of ovulation which was better than that obtained at 16 h. We suggest that the use of GnRH in embryo collection programmes appears justified and is likely to improve embryo yields due to improved rates of fertilization.     

Validation of radioimmunoassays for LH and FSH in the sooty mangabey (Cercocebus atys): Characterization of LH and the response to GnRH

Heterologous radioimmunoassays (RIA) for macaque LH and FSH were validated for the measurement of these hormones in the sooty mangabey and mangabey pituitary LH was characterized relative to rhesus monkey LH. Dilutions of a pituitary mangabey extract and a partially purified preparation of mangabey LH ran parallel to a rhesus monkey standard (LER 1909-2) in the ovine-ovine (o-o) LH assay but showed some deviation from parallelism in the rhesus monkey FSH assay. The LH potency of the mangabey extract and standard were six and 190 times more potent, respectively, than LER 1909-2 in the LH RIA. Mangabey LH was estimated to have a molecular weight of 40,000–42,000 daltons vs 35,000–38,000 daltons for rhesus LH on Sephadex G-100 chromatography. Plasma levels of radioimmunoreactive LH, FSH, and testosterone were assayed before and after a bolus administration of 25, 50, or 100 μg synthetic go-nadotropin releasing hormone (GnRH) to adult male mangabeys. A significant increase in serum levels of LH was seen within 30 min with levels more than fourfold higher than the basal level of LH after administration of 100 μg GnRH. However, no consistent increases in plasma FSH values were detected. The integrated mean LH response above preinjection levels following 25, 50, or 100 μg GnRH was dose related. Serum levels of testosterone were also elevated after administration of GnRH, but peak concentrations of testosterone lagged behind peak levels of LH by approximately 30 min. These studies indicate that the heterologous RIAs may be used for measuring gonadotropins in the mangabey and that the male mangabey is apparently more sensitive to GnRH than the rhesus monkey.     

Developmental patterns of FSH and LH in female rats deprived of light before puberty.

Plasma FSH and LH levels were examined in female rats reared in the dark at different ages from birth until sexual maturation to investigate whether, and to what extent, external factors such as light, influence gonadotropin levels during development. Control animals were raised in diurnal lighting consisting of 12 hours of light and 12 hours of dark. Light deprivation did not eliminate the characteristic peak of gonadotropins seen in early postnatal development but significantly increased levels of FSH and slightly decreased levels of LH (except for a transient rise at day 12). Constant darkness tended to lower whole body, ovarian and pituitary weights but to increase pineal weight. Whereas the time of eye-opening was the same in control and light-deprived animals, puberty (as judged by vaginal opening and first ovulation) was delayed in animals raised in the dark. The data suggest that environmental light has a mediating action on patterns of gonadotropin release, particularly on FSH, during prepuberal development.