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Biomedical subjects

E Nieschlag

Publications and source records attributed to E Nieschlag.

At least 19 recordsLinked to original sources

Molecular cloning of a truncated isoform of the human follicle stimulating hormone receptor.

Northern blot hybridization of human testicular poly (A)+ RNA to a human follicle stimulating hormone receptor probe revealed the existence of multiple mRNA transcripts. In order to investigate whether alternative splicing of the receptor occurs in the human testis we amplified the extracellular and the transmembrane domain of the human testicular follicle stimulating hormone receptor by reverse transcription polymerase chain reaction and subcloned the resulting DNA fragments. Sequence analysis of the recombinant clones revealed the existence of a truncated isoform of the human follicle stimulating hormone receptor which is spliced through a cassette exon mode without a change in the open reading frame, thereby deleting exon IX from the coding region of the receptor.

Amino Acid Sequence

Sulfhydryl oxidase immunoreactivity in seminiferous tubules of infertile men.

Sulfhydryl oxidase (SOx) immunoreactivity was investigated in the seminiferous epithelium of human biopsy material from the testes of 33 adult men with disturbed fertility. SOx immunoreactivity was expressed in normal seminiferous epithelium in type-A spermatogonia (27 +/- 4% of all spermatogonia) (n = 4), in spermatocytes and round spermatids. Mature spermatozoa as well as Sertoli cells were unlabelled. Within the interstitium, Leydig cells were immunopositive. In biopsies of oligozoospermic men showing hypospermatogenesis (n = 24), an increase in labelled spermatogonia up to more than 90% was observed in biopsies, where seminiferous epithelia revealed only spermatogonia and Sertoli cells. Within the group of oligozoospermic patients there was a significant increase of labelled spermatogonia from 43 +/- 13% (greater than 20 mill/ejaculate) (n = 7) to 55 +/- 16% (less than 20 and greater than 10 mill/ejaculate) (n = 6) to 68 +/- 8% (less than 5 mill/ejaculate) (n = 11) and a significant (P = 0.01) decrease of score count from 7.0 +/- 2.7 to 2.0 +/- 1.8. In this group the increase of labelled spermatogonia was correlated with sperm concentrations in the ejaculate (correlation coefficient: r = -0.6). In biopsies of azoospermic patients showing maturation arrest at the level of spermatocytes or spermatids (n = 5) the percentage of labelled spermatogonia was within the range of 24% to 59%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The gonadotropin-releasing hormone (GnRH) agonist-induced initial rise of bioactive LH and testosterone can be blunted in a dose-dependent manner by GnRH antagonist in the non-human primate.

Gonadotropin-releasing hormone (GnRH) agonists induce a clinically undesirable, transitory but very pronounced initial rise of gonadotropin and gonadal steroid secretion. We investigated, in a non-human primate model, whether the initial stimulatory effects of GnRH agonists can be avoided by a short period of pretreatment and simultaneous treatment with a GnRH antagonist. Three groups of five adult male cynomolgus monkeys (Macaca fascicularis) received a single s.c. biodegradable implant loaded with the GnRH agonist, buserelin ([D-Ser(TBu)6-desGly-NH2]-GnRH), releasing approximately 50 micrograms buserelin daily. From 1 week before to 1 week after inception of administration of GnRH agonist, group 1 received the GnRH antagonist vehicle, and groups 2 and 3 were given s.c. injections of the GnRH antagonist Nal-Glu ([Ac-D-Nal(2)1,D-4-Cl-Phe2,D-Pal3,D-Arg5,D-Glu6(AA),D- Ala10]-GnRH) at a dose of 450 or 2250 micrograms/kg daily. In the absence of GnRH antagonist, the GnRH agonist induced a marked elevation of serum luteinizing hormone (LH) and testosterone lasting for 2 and 5 days, respectively. In group 2, Nal-Glu reduced basal hormone secretion and delayed the peak of GnRH-agonist-induced hormone secretion by 1 day. In group 3, the GnRH-agonist-induced rise of LH and testosterone was prevented in three animals and did not exceed baseline hormone levels in the other two animals. Areas under the LH and testosterone curves were significantly reduced in group 3 compared to group 1. After withdrawal of the GnRH antagonist, a second transient rise of hormone secretion was observed. Except for testosterone in group 2, this rise did not exceed the baseline range of hormone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

FSH receptor mRNA is expressed stage-dependently during rat spermatogenesis.

In situ hybridization was performed on testicular tissue from adult male Sprague-Dawley rats using cRNA antisense and sense probe of the monkey FSH receptor (FSHR) cDNA to determine the cellular site of synthesis, and possible stage-dependent expression of FSHR mRNA during the cycle of the seminiferous epithelium. Using antisense probe specific binding was first detected in Sertoli cells just prior to sperm release at stage VIII. The strongest specific hybridization signal was found during stages IX and X followed by a decrease of signal intensity in stages XI-XII. No specific binding was found in stages XIII-VII. The sequence of events with the maximum expression of FSHR mRNA in Sertoli cells in stages IX and X, before FSH-binding and FSH-stimulated cAMP production reach maximum values, coincides with a new wave of spermatogenesis and indicates an effect of FSH and spermatogenic cells on the regulation of FSHR mRNA expression.

Animals

Cyclic corticosteroid immunosuppression is unsuccessful in the treatment of sperm antibody-related male infertility: a controlled study.

In this double blind cross-over study, 20 infertile men, who had sperm antibodies detected by the mixed antiglobulin reaction (MAR test) in the ejaculate and by the tray agglutination test (TAT) in serum, were treated with 40 mg/day prednisolone or placebo from days 1 to 10 of the partners' menstrual cycle. Patients were randomly allocated to different treatment groups. While group 1 started with placebo followed by verum for three consecutive cycles, group 2 began with verum and continued with placebo. All patients had regular intercourse (n = 19) or intra-cervical insemination at ovulation (n = 1). A post-coital test or a sperm penetration test was performed during verum and placebo regimes. Blood samples were drawn from the male partner at this time to control the efficacy of prednisolone treatment by checking the TAT titre. No pregnancy occurred during prednisolone or placebo treatment. In eight of 12 patients, post-coital testing showed little improvement and antibody titres decreased in seven of 16 patients. Side-effects from medication were reported by eight patients (seven verum and one placebo cycle) and caused treatment to be discontinued in two cases. Five patients' partners conceived at a later stage by intrauterine insemination with spermatozoa prepared by 'swim up' (n = 3) or by in-vitro fertilization (IVF n = 2). Thus high dose corticosteroid therapy was ineffective in achieving pregnancies induced by infertile men positive for antisperm antibodies. Since side-effects of corticosteroids should not be underestimated in otherwise healthy men, other reproductive techniques such as intrauterine insemination or IVF should be offered to such couples.

Adult

Interdependent influence of follicular fluid oestradiol concentration and motility characteristics of spermatozoa on in-vitro fertilization results.

Methods are presented for an objective assessment of the quality of both gametes in an in-vitro fertilization programme. The concentrations of oestradiol and progesterone in follicles whose oocytes did or did not fertilize, were measured and assessed as potential markers of oocyte maturity. There was no difference in the mean concentrations of either steroid in follicular fluid of fertilized and unfertilized oocytes. However, a highly significant inverse correlation was observed between the oestradiol concentration in follicles of oocytes becoming fertilized and the number of spermatozoa added for fertilization (P less than 0.001). Follicular fluid concentrations of progesterone did not correlate with the number of inseminated spermatozoa. The correlation between follicular oestradiol concentrations and the number of spermatozoa needed for fertilization was then used to identify movement characteristics of spermatozoa in the culture medium which were relevant for fertilization. Sufficient numbers of spermatozoa having specific values of head cross frequency, lateral head displacement, linearity and curvilinear velocity were critical for the occurrence of fertilization in vitro.

Adult

Effect of testosterone deprivation on expression of the androgen receptor in rat prostate, epididymis and testis.

Adult rats were treated with ethane dimethane sulphonate (EDS) to eliminate the Leydig cells. This treatment resulted in very low levels of testosterone in the blood and in the testis. Furthermore, histological evaluation of spermatogenesis showed no marked differences between control and EDS-treated animals. In the ventral prostate, 5 days after EDS-treatment, a 4.0 +/- 0.3-fold up-regulation of androgen receptor (AR) mRNA was observed, together with a 2.2 +/- 0.2-fold increase in actin mRNA. In the epididymis, a 2.0 +/- 0.5-fold increase in AR mRNA level was observed, without a change in actin mRNA level. In the testes of EDS-treated rats, the AR mRNA level was not changed (1.02 +/- 0.17-fold of controls), and there was also no change in actin mRNA level at 5 days after EDS-treatment. These results indicate that AR mRNA expression in the ventral prostate and epididymis is regulated differentially by testosterone when compared to regulation in the testis. Testicular androgen binding sites were assayed by Scatchard analysis of the binding of 3H-R1881 to a nuclear fraction, that was isolated by a method which involved the use of liquid nitrogen and high sucrose buffer. The number of specific binding sites per testis in EDS-treated rats with testosterone-implants, remained unaltered compared to control rats (9.1 +/- 1.4 pmol/testis). In these rats, 20% of the normal testicular testosterone level was sufficient to maintain the androgen receptor in a tight nuclear binding (transformed) form. In testes from EDS-treated rats without testosterone-implants, the AR did not fractionate into the nuclear fraction; however, the total testicular AR content in these animals was close to control levels, as measured by nuclear 3H-R1881 binding after receptor transformation through injection of a high dose of testosterone (10 mg) 2 h before killing the rats (testosterone pulse). In the different experimental groups, FSH was not required to maintain the total testicular AR content (ligand binding). Immunoprecipitation and Western blotting of the testicular AR using specific monoclonal and polyclonal antibodies indicated that the total testicular amount of immunodetectable AR protein in long-term testosterone deprived rats was very low when compared to that in control rats or rats with testosterone-implants. This is in disagreement with results obtained in the ligand binding assay, and may point to a structural modification of the AR in the testis that possibly occurs in the prolonged absence of androgens.

Animals

Subnormal sperm parameters in conventional semen analysis are associated with discrepancies between fertilization and pregnancy rates in in-vitro fertilization and embryo transfer.

Three hundred and twenty-eight consecutive treatment cycles in 168 couples were analysed retrospectively in order to examine the influence of conventional semen analysis results on the outcome of in-vitro fertilization and embryo transfer with respect to the occurrence of both fertilizations and pregnancies. All treatments were performed under maximally standardized and controlled conditions. Each of the three main determinants of the spermiogram, namely the concentration, motility and morphology of sperm in seminal plasma, was of significant importance for fertilization and subsequent pregnancy. Best correlations were achieved by counting the number of progressively (a+b) motile sperm and the number of normally formed sperm in seminal plasma. The pregnancy rate was reduced significantly in cases in which the sperm concentration was < 10 x 10(6) ml-1 (P < 0.01), or in which there was < 40% progressively motile sperm (P < 0.001), or < 30% normally formed sperm (P < 0.001). If more than one parameter in the spermiogram was abnormal, the fertilization rate depended mainly on the most disturbed sperm parameter. The implantation rate as well as the pregnancy rate was reduced significantly in patients with low progressive sperm motility and normal morphology rates. The difference could only be attributed partially to the lower number of embryos replaced. In conclusion, subnormal sperm quality seems to interfere with developmental stages beyond the process of fertilization.

Adult

Pattern of pineal melatonin concentrations during prolonged exposure to short photoperiods in photosensitive and photoinsensitive Djungarian hamsters.

In the Djungarian hamster (Phodopus sungorus) there is strong evidence that the nightly decompression or lengthening, respectively, of the pineal melatonin pattern is involved in conveying the inhibitory influence of short photoperiods. Some hamsters, however, are insensitive to photoinhibitory influences; other late-responding hamsters show a delayed reaction of several months. The daily pattern of pineal melatonin proves that the mechanisms determining long- or short-day patterns become effective in the morning and evening hours when melatonin concentrations of photoinhibited hamsters are clearly elevated, while those of long-day hamsters are reduced to negligible low values. At two decisive time points in the morning and evening, male and female early-responding photosensitive hamsters were killed after 5, 10, 15, and 20 weeks in short photoperiods, nonresponding hamsters after 10 and 20 weeks, and late-responding after 20 weeks. In all early-responding hamsters changes in gonadal stage, body weight, and pelage color corresponded to the decompression of the nightly melatonin pattern. During prolonged exposure to short photoperiods a decrease of mean melatonin concentrations in the morning and an increase of evening concentrations was observed in both sexes. The lengthening of nightly elevated melatonin concentrations was missing in photoinsensitive hamsters. In late-responding hamsters this decompression seems to be delayed, as melatonin concentrations of female late responders indicate. In conclusion, the lengthening of the melatonin pattern seems to predict a photoperiodic reaction of the effector system. The lengthened pattern of photosensitive hamsters may not be unchangeable, as it may be subjected to modifications during prolonged exposure to short photoperiods.

Animals

Interruption of nocturnal pineal melatonin synthesis in spontaneous recrudescent Djungarian hamsters (Phodopus sungorus).

The duration of nighttime synthesis of the pineal hormone melatonin is believed to determine the breeding season in many mammalian species. Hamsters exposed to short days undergo gonadal involution followed by a return to normal function, suggesting a developed insensitivity to regressive photoperiods. This recrudescence may be due to either exhaustion of the pineal or to target-desensitization. Both theories have been tested previously but failed to explain this phenomenon. We performed an experiment in the Djungarian hamster (Phodopus sungorus), a well-characterized photosensitive species with a type C melatonin pattern (prolonged peak during majority of dark phase), in an attempt to resolve this issue. Among age-matched male hamsters exposed to short days for either 16 weeks (involuted) or 38 weeks (spontaneous recrudescent), marked phase differences in diurnal pineal melatonin rhythms were observed. Furthermore, in recrudescent hamsters the melatonin pattern was divided into two parts, possibly no longer recognizable as a typical short-day rhythm.

Animals

The role of growth hormone and insulin-like growth factor I in the regulation of male reproductive function.

Animal experiments and clinical studies on the interactions between growth hormone (GH) and the male hypothalamic-pituitary-gonadal axis have predominantly concentrated on GH and sex steroid interactions in the regulation of growth and development, or on the metabolic effects of GH. In contrast, little attention has been paid to the possible effects of GH on spermatogenesis, although the first report dealing with this topic was published almost 30 years ago. The interactions of GH and its main mediator, insulin-like growth factor I (IGF-I), with the hypothalamic-pituitary-gonadal axis, and their role in spermatogenesis have recently been investigated using in vitro systems and different animal models (mice and rats). Using Leydig and Sertoli cell cultures, complex interactions between GH/IGF-I and the gonadotropins affecting differentiated cell functions, e.g. steroidogenesis and cell division, have been demonstrated at the cellular level. In vivo studies using immature and mature hypophysectomized rats and GH-deficient mutant male mice and rats indicate that IGF-I can play an important role in the regulation of steroidogenesis and spermatogenesis. Furthermore, although follicle-stimulating hormone and luteinizing hormone are the major regulators of testicular IGF-I production, GH may play an indirect role by potentiating the actions of the gonadotropins in regulating testicular IGF-I content. A large proportion of men presenting at male-infertility clinics are diagnosed as having idiopathic infertility. Further studies are necessary to investigate whether defects associated with GH and/or IGF-I effects in the testis are the cause of male infertility in a small group of these patients.

Animals

Depot gonadotropin-releasing hormone agonist blunts the androgen-induced suppression of spermatogenesis in a clinical trial of male contraception.

Thus far, when tested as male contraceptives, GnRH agonists in combination with androgens were not very effective in producing azoospermia. Since in previous studies androgens were always given simultaneously with the GnRH agonist or later, we tested whether GnRH agonist administration after an initial androgen suppression phase might yield better results. After a control period, 3 groups of young healthy men (n = 8/group) received an initial loading dose of 400 mg 19-nortestosterone hexyloxyphenylpropionate (19NT-HPP), followed by 200 mg of the ester every 3 weeks for 24 weeks. One week after the first 19NT-HPP injection, 2 groups were given a single sc implant injection of 3.3 or 6.6 mg of the GnRH agonist buserelin, respectively, whereas a placebo implant was given to the third group. In the group receiving only 19NT-HPP, serum LH and FSH were markedly suppressed and remained low during the treatment phase. In the 16 volunteers receiving the buserelin implant LH and FSH were also suppressed on day 7, followed by a marked increase in the gonadotropins up to 2 weeks after buserelin implant injection. While LH was consistently suppressed for the remaining treatment phase, FSH returned to almost normal values in weeks 9-15. In contrast to the group treated with 19NT-HPP alone, in which sperm concentrations were reduced to oligozoospermia after only 3 weeks of treatment, the first suppressive effect in the 19NT-HPP/buserelin-treated groups was not seen before week 9. After 30 weeks, when the maximal suppression of spermatogenesis was seen, 4 of 8 volunteers in the group treated with 19NT-HPP alone were azoospermic, and the remaining 4 volunteers were oligozoospermic. In the groups treated with 19NT-HPP/buserelin, no more than 4 of 16 volunteers were azoospermic, and no more than 8 of 16 volunteers were oligozoospermic at any time point. It is concluded that GnRH agonist depot preparations have a blunting effect on the suppression of pituitary and testicular function caused by androgens in men participating in contraceptive trials.

Adult

Effective suppression of luteinizing hormone and testosterone by single doses of the new gonadotropin-releasing hormone antagonist cetrorelix (SB-75) in normal men.

In rats and nonhuman primates the new GnRH antagonist cetrorelix (SB-75; [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,D-Cit6,D-Ala10]GnR H) has been shown to suppress testosterone secretion effectively and persistently. A clinical phase I study was performed to assess the hormonal effects of this highly potent antagonist in normal men. After 2 control examinations 30 young male volunteers were randomly assigned to 6 treatment groups (n = 5/group), and single doses of 0 (placebo), 0.25, 0.5, 1.0, 2.0, and 5.0 mg cetrorelix were administered sc. Blood samples were obtained over the course of 7 days postinjection. After maximal cetrorelix serum levels were achieved 1 h postinjection, the GnRH antagonist serum levels decreased with a terminal t1/2 of 29.8 +/- 4.2 h (mean +/- SE). LH secretion was suppressed dose- and time-dependently; maximal suppression occurred 4-6 h postinjection. Suppression of FSH did not reach statistical significance. Doses of 1.0, 2.0, and 5.0 mg cetrorelix significantly suppressed testosterone secretion compared to that in the placebo group. After the administration of 1.0 mg cetrorelix, maximal suppression was seen 8 h after injection, with testosterone levels of 7.5 +/- 1.1 nmol/L compared to 15.8 +/- 2.2 nmol/L in the placebo group. Maximal testosterone suppression by 2.0 and 5.0 mg cetrorelix occurred 12 h after injection, with testosterone concentrations of 4.9 +/- 0.5 and 2.2 +/- 0.4 nmol/L, respectively, compared to 16.5 +/- 1.7 nmol/L in the placebo group. Twenty-four hours after the injection of 1.0 and 2.0 mg cetrorelix, testosterone values were no longer significantly different from those in the placebo group, whereas in the 5.0-mg dose group testosterone concentrations increased slightly and reached serum concentrations in the lower normal range after 48 h. The only side-effect observed after the administration of cetrorelix was a transient local erythema at the injection site that disappeared within 30 min. No local induration or pruritus, or any adverse systemic side-effect occurred in any volunteer. In conclusion, the new GnRH antagonist cetrorelix effectively decreases serum LH and testosterone concentrations in a dose- and time-dependent manner and, therefore, has potential for treatment of sex hormone-dependent diseases and male contraception.

Follicle Stimulating Hormone

Testosterone buciclate (20 Aet-1) in hypogonadal men: pharmacokinetics and pharmacodynamics of the new long-acting androgen ester.

Due to unfavorable pharmacokinetics of the available androgen esters for substitution therapy of male hypogonadism, there is a demand for new testosterone (T) preparations producing constant serum levels in the physiological range. To assess the pharmacokinetics and pharmacodynamics of the new ester testosterone buciclate (TB) [20 Aet-1] in hypogonadal men a clinical phase I-study was performed. After two control examinations 8 male patients with primary hypogonadism were randomly assigned to 2 treatment groups (n = 2 x 4) given single doses of either 200 (group I) or 600 mg (group II) TB im. Blood samples were obtained 1, 2, 3, 5, and 7 days post injection and then weekly in the course of 4 months. In group I serum androgen levels did not rise to normal values. However, in group II androgens increased significantly and were maintained in the normal range up to 12 weeks with maximal serum levels of 13.1 +/- 0.9 nmol/L (mean +/- SE) in study week 6. No initial peak release of T was observed in either study group. Pharmacokinetic analysis revealed a terminal elimination t1/2 beta of 29.5 +/- 3.9 days and a mean residence time of 65.0 +/- 9.9 days in group II. In one patient in group II dihydrotestosterone levels slightly exceeded the upper normal limit during the study course. Sex hormone-binding globulin remained unchanged and estradiol serum levels never exceeded the normal range in any patient. In group II gonadotropins were significantly suppressed, whereas no change was seen in group I. A significant increase in body weight, hematological parameters, and libido/potency was observed after TB injection which was more pronounced in the higher dose group. Regardless of the dose administered, no significant change was seen in uroflow, prostate volume measured by transrectal ultrasonography, or prostate specific antigen. No adverse side-effects including changes in clinical chemistry were observed. In conclusion, single injections of 600 mg TB in hypogonadal patients show favorable pharmacokinetics and pharmacodynamics. This new long-acting T ester is a promising new agent for substitution therapy of male hypogonadism and for male contraception.

Adult

Microheterogeneity of pituitary follicle-stimulating hormone in male rats: differential effects of the chronic androgen deprivation induced by castration or androgen blockade.

Testicular androgens are known to influence not only the secretion but also the bioactivity and molecular composition of pituitary FSH. In the present study, we investigated the effects of chronic androgen blockade and castration on the molecular heterogeneity of the gonadotrophin. Groups of male adult rats (five animals per group) received one of the following treatments: vehicle, the non-steroidal anti-androgens casodex (20 mg/kg per day) or flutamide (20 mg/kg per day), or castration. After 8 weeks, the animals were killed and individual pituitary homogenates fractionated by isoelectric focusing (IEF) on sucrose density gradients in the pH range 2.5-8. FSH was measured by radioimmunoassay (RIA) in the individual fractions and by invitro bioassay (Sertoli cell aromatase bioassay) in pools of fractions which were combined according to pH intervals of 0.5 units. Bioactive and immunoreactive FSH were also measured in sera and unfractionated pituitary extracts. Testosterone and inhibin were assayed in sera by RIA. A significant increase in serum immunoreactive and bioactive FSH was demonstrated in flutamide-treated and castrated animals, whereas the pituitary content of bioactive FSH remained unchanged in the four groups. Serum testosterone and inhibin were undetectable in castrated animals and significantly increased in those treated with flutamide. By RIA, the IEF profiles of the flutamide-treated and castrated rats showed a significant reduction of the FSH isoforms with 3.5 < pI < 4, with a significant increase in the isoforms with pI > 4 only in the castrated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen Antagonists

Exogenous gonadotrophin-releasing hormone (GnRH) stimulates LH secretion in male monkeys (Macaca fascicularis) treated chronically with high doses of a GnRH antagonist.

We reported previously that after a single injection of a gonadotrophin-releasing hormone (GnRH) antagonist to male monkeys, exogenous GnRH stimulated LH secretion in a time- and dose-dependent manner, indicating that GnRH antagonist-induced blockade of LH secretion resulted from pituitary GnRH receptor occupancy. The present study was performed to investigate whether GnRH can also restore a blockade of LH and testosterone secretion during chronic GnRH antagonist administration. Four adult male cynomolgus monkeys (Macaca fascicularis) received daily s.c. injections of the GnRH antagonist [N-Ac-D-pCl-Phe1,2,D-TRP3,D-Arg6-D-Ala10]-GnRH (ORG 30276) at a dose of 1400-1600 micrograms/kg for 8 weeks. Before the GnRH antagonist was given and during weeks 3 and 8 of treatment, pituitary stimulation tests were performed with 0.5, 5, 50 and 500 micrograms synthetic GnRH, administered in increasing order at intervals of 24 h. At 8 weeks, a dose of 1000 micrograms GnRH was also given. All doses of GnRH significantly (P less than 0.05) stimulated serum concentrations of bioactive LH (3- to 8-fold) and testosterone (2.6- to 3.8-fold) before the initiation of GnRH antagonist treatment. After 3 weeks of GnRH antagonist treatment, only 50 and 500 micrograms GnRH doses were able to increase LH and testosterone secretion. Release of LH was significantly (P less than 0.05) more elevated with 500 micrograms compared with 50 micrograms GnRH. After 8 weeks, only the highest dose of 1000 micrograms elicited a significant (P less than 0.05) rise in LH secretion. Basal hormone levels just before the bolus injection of GnRH were similar (P greater than 0.10-0.80).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals