Effects of TAP-144-SR, a sustained-release formulation of a potent GnRH agonist, on experimental endometriosis in the rat

A new, simple experimental endometriosis model was established by auto-transplanting endometrial tissue fragments beneath kidney capsules in female rats. The transplanted endometrial tissue grew well, forming a fluid-filled cyst, which reached maximal size 2 to 3 weeks after transplantation. The growth and maintenance of the transplants was dependent on the ovary: ovariectomy induced regression of well grown transplants. The therapeutic effects of TAP-144-SR (biodegradable microcapsules of copoly (DL-lactic/glycolic acid) copolymer containing a potent GnRH agonist, TAP-144 (D-Leu6-[des-Gly10-NH2]-GnRH ethylamide, leuprolide acetate) were studied with this rat endometriosis model. A single sc injection of TAP-144-SR (corresponding to 1, 10 or 100 micrograms/kg/day of TAP-144), suppressed the growth of the transplanted endometrial tissues and uterine weight in a dose-dependent manner. At 100 micrograms/kg/day, the suppressive effect was more marked in rats given TAP-144-SR than in those given TAP-144 solution. The extent of suppression was comparable to that caused by ovariectomy. Serum and pituitary concentrations of LH and FSH were also reduced more markedly by the administration of TAP-144-SR than by TAP-144 solution. From these results, the present endometriosis model was found to be useful for the evaluation of compounds with potential therapeutic activity. The sustained-release formulation of TAP-144 seems to be beneficial over its solution in terms of both convenience and efficiency for therapy of patients with endometriosis.     

Endocrinological studies on TAP-144-SR, a sustained-release formulation of a potent GnRH agonist (D-Leu6-[des-Gly10-NH2]-GnRH ethylamide), in male rats

The paradoxical effects of TAP-144-SR, a biodegradable sustained-release formulation of a potent GnRH agonist (TAP-144, leuprolide acetate) were evaluated in male rats by comparing its potency with that of TAP-144 solution. A single sc injection of TAP-144-SR (equivalent to 0.1 mg/kg/day as TAP-144), prepared by encapsulating the agonist in microcapsules of copoly (DL-lactic/glycolic acid), suppressed serum levels of androgens, and the levels remained suppressed for 4 weeks. The potency of the paradoxical effects of TAP-144-SR was evaluated 4 weeks after treatment by comparing it with that of TAP-144 solution administered daily for 4 weeks. Both daily injections of TAP-144 solution and a single injection of TAP-144-SR (equivalent to 0.02, 0.2 or 2 mg/kg/day as TAP-144) decreased the weight of the testes, prostates and seminal vesicles in a dose-dependent manner in a 4-week assay in male rats. TAP-144-SR was more effective than TAP-144 solution in reducing these organ weights. Serum and pituitary concentrations of LH and FSH and serum testosterone levels were also lower in TAP-144-SR-treated than in TAP-144 solution-treated rats. These results indicate that the paradoxical effects were more extensive upon TAP-144-SR treatment, suggesting that maintaining constant serum TAP-144 levels results in more extensive desensitization of the pituitary and testes. These results also suggest advantages of TAP-144-SR over TAP-144 solution in both efficacy and convenience as an anti-prostatic tumor agent.     

Treatment of central precocious puberty with an LHRH agonist (Buserelin): effect on growth and bone maturation after three years of treatment

The LHRH analog Buserelin was used to treat 27 children (21 girls, 6 boys) with central precocious puberty. Nineteen patients had idiopathic precocious puberty and 8 had organic lesions (hamartoma, hydrocephalus or suprasellar arachnoid cyst). All patients received 20 or 30 micrograms/kg/day s.c. of Buserelin, and we obtained plasma E2 less than 20 pg/ml, vaginal maturation index less than 30 in girls or plasma testosterone less than 0.3 ng/ml in boys. The mean growth rate decreased from 9.3 +/- 0.5 to 4.6 +/- 1.3 cm/year after 3 years. The velocity of skeletal maturation decreased so that the final height prediction improved by a mean value of 1.6 SD. As the follow-up increases, this study confirms that LHRHa therapy is effective and potentially improves the final height of children presenting active and severe central precocious puberty.     

Treatment of precocious puberty with a long-acting preparation of D-Trp6-LHRH

D-Trp6-LHRH was tested in 6 girls 1-8 years old and 7 boys 2-10 years old with precocious puberty. All children had advanced bone age, breast or testis enlargement and a pubertal LH response to LHRH. 60 micrograms LHRH-A/kg body weight was given intramuscularly on days 1 and 21 and thereafter every 4 weeks for 6-21 months. In girls, breast enlargement disappeared and mean uterus size decreased within 6 months. Mean ovary length decreased from 25.0 +/- 1.9 to 16.0 +/- 2.7 (p less than 0.02). In boys, mean testis volume decreased from 8.0 +/- 1.1 to 6.7 +/- 1.4 ml (p less than 0.05) within 6 months. In both sexes, growth velocity decreased significantly and bone maturation was reduced. Plasma levels of estradiol or testosterone and FSH levels decreased significantly within 3 weeks. The LH response to LHRH was reduced to normal prepubertal values after 7 weeks. No secondary clinical or biochemical escape occurred. No side effects occurred except for transient vaginal bleeding in one girl after the first and second injection. No antibodies to LHRH-A were detected in the patients' sera. This study demonstrates the ability of a delayed release formulation of D-Trp6-LHRH to suppress pituitary and gonadal secretion and pituitary response to LHRH for as long as 2 years of therapy. This treatment appears to be more efficient in treating both clinical and biochemical abnormalities than does treatment with inhibitory steroids. Additionally the method of administration is more practical and ensures better patient compliance.     

Diagnostic utility of a low-dose gonadotropin-releasing hormone test in the context of puberty disorders

OBJECTIVES: The 10-microg gonadotropin-releasing hormone (GnRH) test assesses pituitary gonadotroph responsiveness, whereas the 100-microg dose assesses maximal secretory capacity. Our aims were to establish normative data for the low-dose test in children and to evaluate the test in diagnosing common pubertal disorders. METHODS: We retrospectively classified 107 children who underwent 10-microg GnRH tests into normal prepubertal (20 boys, 10 girls), normal early pubertal (10 boys, 16 girls), constitutional delay of puberty (CDP, 13 prepubertal boys >12 years), hypogonadotropic hypogonadism (HH, 5 prepubertal boys >12 years), central precocious puberty (CPP, 19 girls) or premature thelarche/variant (13 girls). RESULTS: Peak LH response was higher in prepubertal boys >12 years compared with younger boys (p < 0.01) but showed no further change in early puberty. CDP boys had LH responses similar to prepubertal boys >12 years. HH boys showed an absent LH response which diagnosed HH with 100% sensitivity and 96% specificity. Thelarche girls had LH:FSH peak ratios lower than normal prepubertal (p = 0.001), pubertal (p < 0.05) or CPP (p = 0.001) girls. CONCLUSIONS: We have established normative values for the low-dose GnRH test in children. The test successfully differentiated HH from CDP in boys, and contributed to the differential diagnosis of CPP and premature thelarche in girls.     

A radioimmunoassay for a highly active luteinizing hormone-releasing hormone analogue and relation between the serum level of the analogue and that of gonadotropin

Antisera to an LH-RH analogue, des-Gly10-[D-Leu6]-LH-RH-ethylamide (TAP-144) were produced in 10 rabbits. By using these antisera, a specific and sensitive radioimmunoassay for TAP-144 was established. Sensitivity of the radioimmunoassay ranged from 5 to 100 per assay tube with these antisera. Lh, FSH, TRH, LH-RH, and the 1-6 fragment of TAP-144 did not practically cross-react with LH-RH analogues, though the degree of the cross-reactivity differed among individual sera. The average cross-reactivity of the 10 antisera showed low specificities to TAP-144 analogues which are altered at positions 2, 3, 4, 5, and 6, but showed high specificities to those altered at positions 8 and 9. The antisera also showed low cross-reactivities to LH-RH analogues replaced at position 6 by D-amino acids and those altered at position 10 by alkylamines, but they showed fairly high cross-reactivities to analogues which are altered simultaneously at both positions 6 and 10. When TAP-144 was administered intraperitoneally to rats on the diestrous day, serum concentrations of TAP-144 increased dose-dependently but maximal serum concentrations of both LH and FSH were attained in response to higher doses of TAP-144. The peak LH and FSH concentrations appeared 70 to 110 min after the peak TAP-144 concentration had been reached. Similar delays in reaching the peak LH and FSH levels were also observed when TAP-144 was administered intravenously, subcutaneously and intramuscularly. When TAP-144 was administered intravaginally, a low but constant serum level of TAP-144 was maintained from 5 to 300 min after the administration, but serum LH and FSH levels declined to a low level from 180 min after the TAP-144 administration.     

Growth, bone maturation and height prediction after three years of therapy with the slow release GnRH-agonist Decapeptyl-Depot in children with central precocious puberty.

More than 100 patients with central precocious puberty are participating in this international multicenter study using monthly i.m. injections of the slow-release GnRH agonist Decapeptyl-Depot. In 15 patients, Decapeptyl-Depot treatment could be discontinued after 2 years of therapy. Gonadal suppression was promptly reversible in all of them, as shown by prepubertal low gonadotrophin- and sex steroid levels. Of the remaining 90 patients, 40 have been treated for more than 3 years, including 33 girls and 7 boys. Plasma levels of LH, FSH, estradiol and testosterone dropped to the prepubertal range after one month of Decapeptyl-Depot and remained there for the whole period of therapy. At start of therapy, mean chronologic age of these 40 children was 6.6 +/- 1.4 (SD) years, mean bone age 10.2 +/- 1.9 years. Mean predicted adult height increased in the boys from 173.6 +/- 13.8 (SD) cm at start of therapy to 184.6 +/- 17.0 cm after 3 years. Predicted adult height increased in girls from 158.0 +/- 12.2 to 161.0 +/- 7.5 cm. Undue side effects were not seen, long term tolerance was good. It is concluded that Decapeptyl-Depot injected i.m. every 4 weeks suppresses the pituitary-gonadal axis in children with central precocious puberty without clinical or biochemical escapes, and leads to an increase in predicted adult height by more than 3 cm in all boys and in 53% of the girls after three years of treatment.     

Long-term results of long-acting luteinizing-hormone-releasing hormone agonist in central precocious puberty.

Thirty children with precocious puberty (24 girls aged 6.5 +/- 2.3 years and 6 boys aged 7 +/- 2.9 years) were treated over 5 years with Decapeptyl. In girls, the menses disappeared, breast enlargement regressed, and uterus and ovary sizes returned to prepubertal values. In boys, a significant decrease of testicular size was observed. Plasma levels of estradiol and testosterone, and basal and post-luteinizing hormone (LH)-releasing hormone (LHRH) LH and follicle-stimulating hormone (FSH) remained in the prepubertal range. Growth velocity decreased after 1 year from 9.7 +/- 3.5 to 5.5 +/- 1.3 cm/year, while the height age/bone age ratio was normalized in both sexes after 3 years. In 15 girls, Decapeptyl was interrupted after 2.3 years. During those 2.3 years, bone age increased from 11.6 +/- 0.8 to 12.5 +/- 0.7 years with a growth velocity of 5.3 +/- 1.8 cm/year. During the year following interruption, height increased from 152.2 +/- 4.9 to 157.7 +/- 4.9 cm (growth velocity 5.5 cm/year) and bone age from 12.5 +/- 0.7 to 13.5 +/- 0.6 years. One year after treatment, plasma levels of estradiol were 106.7 +/- 84.7 pg/ml, of LH, 25.5 +/- 17.6 mIU/ml, and of FSH, 10.8 +/- 5.9 mIU/ml. Menses appeared in 13 girls. Moreover, 18 months after interruption, bone age was 13.9 +/- 0.6 years and height 159.5 +/- 5.2 cm, being significantly superior to the final height of a historical control group: 151.5 +/- 4.8 cm (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Gonadotropin pulsatile secretion in girls with premature menarche

Five prepubertal girls (2.3-8.1 years old) were studied for isolated or recurrent vaginal bleeding in the absence of other signs of precocious puberty (premature menarche). Four of these girls with recurrent vaginal bleeding were studied for pulsatile gonadotropin secretory patterns. During sleep 3 girls showed luteinizing hormone (LH) pulses with low amplitude and a pubertal pattern of frequency whereas follicle-stimulating hormone (FSH) increased without demonstrable episodic secretion. Luteinizing hormone-releasing hormone (LHRH) tests demonstrated that FSH responses are greater than the LH responses, as in prepuberty. In 3 cases estradiol levels had augmented above normal prepubertal range. The menses spontaneously stopped during the follow-up. A reevaluation of the gonadotropin pattern, having the menses stopped for 6 months, in one of the girls with pulsatile LH secretion showed an apulsatile prepubertal LH pattern. Also estradiol levels returned to prepubertal range. A follow-up of 10-66 months of these patients did not show any growth and bone acceleration or signs of precocious puberty. Our data suggest that in premature menarche a partial and transient activation of hypothalamo-pituitary axis could be present. Premature menarche seems to be a benign and self-limiting condition and one of the girls had a normal onset of puberty during follow-up.     

Serum leptin concentration and its effect on puberty in Naqu Tibetan adolescents

This study aimed to clarify the regularity of leptin in Naqu Tibetan adolescents. This study investigated the concentration of fasting serum leptin and clarified its relationship between BMI and other indices. Healthy Naqu Tibetan adolescents aged 12-18 were investigated randomly in the study. They were divided into seven groups (each year as one group, 12 boys and 12 girls in each group); serum concentrations of leptin, estradiol, testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were analyzed. The height and body weight of the 168 healthy Naqu Tibetan adolescents were also assessed. The leptin level in boys decreased with age but increased in girls; in boys and girls they both differed between groups (p<0.05). In boys, the leptin level was inversely correlated with body mass index (BMI), FSH, and T (p<0.05), while in girls, it was positively related to BMI, FSH, LH, and E2 (p<0.01).These findings suggested that during puberty the serum leptin concentration increased with age in girls while it decreased in boys; in the same age group, the leptin level in girls was significantly higher than in boys. Leptin may have some relationship with puberty in Tibetan adolescents.     

Puberty due to ectopic HCG production in a girl with suprasellar ectopic pinealoma associated with panhypopituitarism

A 13.5-year-old girl who developed puberty due to HCG production by suprasellar ectopic pinealoma was reported. This girl appeared to be in a state of precocious puberty at the age of 5 when ectopic pinealoma was first diagnosed. Her breasts started to develop at 13 years of age in spite of hypopituitarism. Plasma LH was found to increase for several months and gave rise to suspicion of the recurrence of the tumor, which was confirmed by the detection of HCG in plasma and CSF. Precocious puberty or puberty can be a characteristic endocrinological manifestation of an HCG producing tumor not only in boys but also in girls. The measurement of plasma HCG (or LH) can be a useful tumor marker in following the clinical course of an HCG producing tumor.     

Plasma concentrations of FSH and LH in entire and castrated prepubertal bull calves treated with Gn-RH.

In bulls there was no increase in plasma FSH and only a small increase in LH over the first 14 weeks of age. In steers (castrated) plasma LH and FSH were unchanged for the first 3 weeks but increased significantly at 7 and 14 weeks. After 100 micrograms Gn-RH, LH release in bulls was minimal until 7 and 14 weeks and there was no comparable rise for FSH. LH and FSH responded to Gn-RH throughout the trial in the steers. The neonatal calf testes selectively inhibited the release of FSH from the pituitary even when challenged with Gn-RH.     

Unilateral cryptorchidism with compensatory hypertrophy of descended testicle in prepubertal boys.

5 prepubertal boys with unilateral cryptorchidism and compensatory hypertrophy of the descended testicle, 22 prepubertal boys with unilateral cryptorchidism and without CTH, and 14 prepubertal normal boys were submitted to LH-RH and to HCG tests in order to study the hormonal behaviour in CTH phenomenon before puberty. High but normal peaks of plasma LH and FSH were observed after LH-RH in CTH boys who showed a significant increase of testosterone after HCG stimulation. On the contrary the LH response to LH-RH and the testosterone response to HCG of the boys with unilateral cryptorchidism and without CTH were, as expected, significantly lower than in the control ones.     

Presentation of 493 Consecutive Girls with Idiopathic Central Precocious Puberty: A Single-Center Study

Background

Despite the number of reported data concerning idiopathic central precocious puberty (CPP) in girls, major questions remain including its diagnosis, factors, and indications of gonadotropin releasing hormone (GnRH) analog treatment.

Methods

A retrospective, single-center study was carried out on 493 girls with CPP.

Results

Eleven girls (2.2%) were aged less than 3 years. Breast development was either isolated (Group 0, n = 99), or associated with one sign, pubic hair development, growth rate greater than 2 standard deviation score (SDS) or bone age (BA) >2 years above chronological age, (Group 1, n = 187), two signs (Group 2, n = 142) or three signs (Group 3, n = 65). The interval between onset of puberty and evaluation, body mass index (BMI) SDS, plasma luteinising hormone (LH) concentrations (basal and peak) and LH/ follicle-stimulating hormone (FSH) peak ratio after GnRH test, plasma estradiol and uterus length were significantly greater in Groups 2 and 3 than in Groups 0 and 1 respectively. 211 (42.8%) patients were obese and/or had excessive weight gain during the year before puberty. Obese girls more often had BA advance of >2 years (p = 0.0004) and pubic hair development (p = 0.003) than the others. BMI did not correlate with LH or with LH/FSH peak ratio. Girls with familial history of early puberty (41.4%) had greater frequencies of pubertal LH/FSH peak ratios (p = 0.02) than the others. During the 31 years of the study, there was no increase in the frequency of CPP or variation in its characteristics.

Conclusion

Obesity is associated with a higher BA advance and higher frequency of pubic or axillary hair development but not with LH secretion, suggesting that obesity accelerates adrenarche but not the maturation of the hypothalamic-pituitary-ovarian axis. The LH/FSH peak ratio was more frequently pubertal in girls with a familial history of early puberty, suggesting that this maturation depends on genetic factors.     

Pituitary and Leydig cell function in boars actively immunized against gonadotrophin-releasing hormone

Crossbred boars were (a) immunized against GnRH conjugated to human serum globulin (200 micrograms GnRH-hSG) in Freund's adjuvant at 12 weeks of age and boosted at weeks 18 and 20 (N = 10), (b) served as controls and received hSG only in adjuvant (N = 10), or castrated at weaning (N = 10). At 24 weeks of age (immediately before slaughter), the boars were challenged with saline or pig LH (1 microgram/10 kg body weight). After slaughter, fresh testicular fragments were incubated with pig LH (0.05 and 0.2 ng/2 ml medium) to assess the effects of immunization on Leydig cell function. Pituitary contents of LH and FSH, and testicular LH receptor content were also measured. The results indicated that plasma LH and testosterone concentrations, pituitary LH content, testicular LH receptor content, testis and sex accessory organ weights were significantly reduced in GnRH-immunized boars compared to hSG-adjuvant controls. However, plasma and pituitary FSH content were not affected by high antibody titres generated against GnRH. The testicular testosterone response to exogenous LH in vivo and in vitro was significantly reduced (P less than 0.05) in GnRH-immunized boars. These results indicate that active immunization against GnRH impairs pituitary and Leydig cell functions in boars.     

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.     

Causes of precocious puberty in children referred for evaluation in hospital conditions

INTRODUCTION: Symptoms of precocious puberty (PP) in children always arouse anxiety in their parents. Many children with PP are being hospitalized for the detailed diagnostic work-up. The aim of our study was to analyze the frequency of the variants of PP in children referred to our department. MATERIAL: Retrospective analysis of 119 children (103 girls and 16 boys) referred for hospitalization in the years 2003-2005 due to signs of precocious puberty was performed. RESULTS: Premature thelarche, benign variant of puberty, was diagnosed in 62 (53%) girls, in the mean age of 3.39 (+/- 2.33) years. Their mean height was within 0.7 +/- 1.1 SD. Premature pubarche was diagnosed 30 (25%) children--22 girls and 8 boys in the mean age was 7.24 (+/- 0.81) years. Their mean height was 1.3 +/- 1.0 SD and was significantly higher than normal (p < 0.0001). Premature menarche was diagnosed in 8 (7%) girls in the mean age 4.81 +/-2.26 years. Mean height in this group was normal for age (0.9+/-0.8 SD). PP was diagnosed in 19 (16%) children (11 girls and 8 boys) in the mean age 5.91 +/- 1.63 years. Mean height in this group was 1.6 +/- 0.7 SD, and was significantly higher than the mean for age (p<0.0005). GnRH-dependent type was present in 15 children, diagnosed as idiopathic in 9 girls and 1 boy. In 5 children (4 boys and 1 girl) pathology of central nervous system was found. In 4 children GnRH-independent precocious puberty was diagnosed--in 3 caused by congenital adrenal hyperplasia and in 1 boy by tumour of testis (leydigioma). CONCLUSIONS: Girls with precocious thelarche without growth acceleration present the benign variant of puberty and need clinical follow up only. Boys with clinical signs of precocious puberty should be carefully evaluated to rule out the organic cause.     

Effect of maternal treatment with altrenogest on age at puberty, hormone concentrations, pituitary response to exogenous GnRH, oestrous cycle characteristics and fertility of fillies

Puberty was studied using 15 fillies of Quarter Horse phenotype. Fillies were from dams treated daily from Days 20 to 325 of gestation with: (1) 2 ml neobee oil per 50 kg body weight (controls); or (2) 2 ml altrenogest (2.2 mg/ml) per 50 kg body weight. The clitoris was measured at birth and approximately every 12 weeks until 84 weeks of age. Blood samples were collected from 9 fillies (5 treated, 4 controls) every 4 days over a 28-day period at 8-week intervals from 4 to 68 weeks of age; sampling continued every 4 days after 72 weeks of age until first oestrus. Blood samples were collected daily during oestrus (greater than or equal to 35 mm follicle) and on Days 4, 6, 10, and 14 after ovulation for the first 2 oestrous cycles. GnRH challenges (5 micrograms/kg) were administered every 8 weeks from 32 to 96 weeks of age. Puberty was defined as the first oestrus with ovulation. Beginning 1 February 1987, fillies were teased daily and their ovaries were examined by ultrasonography every 3 days (daily during oestrus). Fillies were inseminated with 500 x 10(6) motile spermatozoa from one stallion. Pregnancy was diagnosed by ultrasonography on Days 11, 12, 15 and every 5 days until Day 50 after ovulation. Prenatal altrenogest treatment caused clitoral enlargement (P less than 0.05) and increased serum concentrations of LH from 1 to 7 months of age. The amount of LH released in response to exogenous GnRH was greater (P less than 0.05) in treated fillies at 32, 64, and 72 weeks of age. Treated fillies had higher serum concentrations of FSH from 1 to 4 months (P less than 0.05), but FSH was lower (P less than 0.05) in treated fillies before and during first oestrus. Serum concentrations of LH and FSH peaked transiently at 10 months and LH was depressed from 64 to 88 weeks and began to rise 14 days before first oestrus. Concentrations of FSH began to decline 14 days before first oestrus. The median age at puberty was 90 weeks. Durations of oestrus, dioestrus, and the oestrous cycle were not different between groups and were similar to those for adult mares. First cycle pregnancy rates and overall rates were 100 and 82% and 100 and 91.7% for control and treated fillies, respectively (P greater than 0.05). Maternal treatment with altrenogest did alter gonadotrophin secretion before puberty, but had no effect on functional reproductive performance in fillies.     

Bioactivity of luteinizing hormone during normal puberty in girls and boys

In order to evaluate the in vitro bioactivity of LH during normal puberty compared to LH immunoactivity measured in a highly sensitive immunoassay, blood plasma samples from healthy children were analyzed in a mouse Leydig cell assay (MLCA). Blood samples were obtained from 60 healthy girls and boys during normal pubertal development. Samples were taken on two occasions with a 1-year interval. Three daytime samples and three nighttime samples were analyzed. The correlation of the LH immunoradiometric assay (IRMA) activity with the LH activity in the MLCA varied from 0.60 to 0.96 in the different pubertal stages. During pubertal development, a gradually increase in the activity of LH in both the IRMA and MLCA was found. The ratio of the in vitro bioactivity compared to the immunoreactivity (B/I ratio) did not change significantly during puberty: it was 0.84 (SD 0.58) and 0.66 (SD 0.40) during the first and second sampling period in girls and 0.88 (SD 0.38) and 0.91 (SD 0.46, NS) in the boys. The B/I ratio of LH does not change during puberty. With a high sensitivity and specificity, measurement of LH by IRMA gives representative measurements of the LH in vitro bioactivity in children during pubertal development. Copyrightz1999S. KargerAG,Basel