Pituitary-testicular function is suppressed by an LHRH antagonist but not by an LHRH agonist in the marmoset monkey

Lunn, S. F.; Dixson, Alan F.; Sandow, J.; Fraser, Hamish M.

doi:10.1677/joe.0.1250233

Cited by 26 publications

(12 citation statements)

References 36 publications

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“…In these studies, neither local testosterone nor supplemented human chorionic gonadotropin (hCG) could induce maturation of the immature testicular tissues of marmoset in nude mice host. Moreover, increased levels of gonadotropin after gonadectomy (Hodges 1978), but failure of gonadotrophin-releasing hormone (GnRH) agonist to stimulate gonadotropin and testosterone concentrations (Lunn et al 1990) further suggest the peculiar endocrine regulation of testicular function in this species as demonstrated previously by us , Müller et al 2004.…”

Section: Introductionmentioning

confidence: 53%

Changes in endocrine profile and reproductive organs during puberty in the male marmoset monkey (Callithrix jacchus)

Chandolia¹,

Luetjens²,

Wistuba³

et al. 2006

Reproduction

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Data on pubertal maturation in male marmoset, a model for human reproduction, are scant and conflicting. We collected data on novel parameters to characterize puberty. Twenty-five marmoset monkeys were assigned to five age groups by weeks (wk): 21 (pre-pubertal), 43 (onset of puberty), 52 (fully pubertal), 70 (mature), and 116 (fully adult). Serum and intratesticular testosterone and pituitary bioactive chorionic gonadotropin (bioCG) were measured. Testicular development was assessed by ultrasonography, histology, and flow cytometry. Three consecutive blood samples revealed extreme fluctuations in testosterone concentrations, suggesting an erratic secretion. Age-related changes in serum testosterone and pituitary bioCG concentrations were observed. Intratesticular androgens (ITAs) showed high fluctuations within groups at all ages and were high in some animals by 21 wk. Unexpectedly, no correlation between pituitary bioCG and serum testosterone or ITAs was found, but these parameters significantly correlated with testicular weight and volume. These observations were consistent a dependence on the testis growth on bioCG. Unfortunately, the low serum levels of bioCG were not measurable in this study. At 43 wk, the animals reached puberty. At 52 wk of age, animals attained maximum body and epididymal weights and qualitatively normal spermatogenesis, but testes continued growing, reaching a maximum of all parameters at 70 wk of age, without further major changes at the age of 116 wk. It is concluded that (1) gonadal activation is evident at wk 21, (2) the male marmoset reaches the pubertal threshold around 43 wk of age, attains qualitative parameters at 52 wk, matures further to sexual maturity at 70 wk, and (3) serum testosterone and ITAs are highly variable without any identifiable correlation with pituitary bioCG.

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Section: Introductionmentioning

confidence: 53%

Changes in endocrine profile and reproductive organs during puberty in the male marmoset monkey (Callithrix jacchus)

Chandolia¹,

Luetjens²,

Wistuba³

et al. 2006

Reproduction

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“…The assay sensitivity was 2-5 pmol/tube and inter-and intra-assay coefficients of variation were 11-1 and 4-2% respectively. Testosterone After extraction, plasma testosterone was measured by RIA as described by Lunn et al (1990). Intra-and interassay coefficients of variation were 4-5 and 11 0% respectively, the assay sensitivity being 50nmol/1.…”

Section: Assays Progesteronementioning

confidence: 99%

“…Assay data were corrected to allow for a mean recovery after extraction of 68%. Minor modifications from the procedure used by Lunn et al (1990) involved the use of an increased plasma volume for extraction (from 10 to 20 pi), all of the extracted plasma samples subsequently being measured in triplicate, rather than in duplicate.…”

Section: Assays Progesteronementioning

confidence: 99%

“…In the male marmoset monkey, administration of the LHRH agonist buserelin, in the form of an implanted rod, caused an initial stimulation of LH release, but subsequent desensitization did not occur, plasma LH and testosterone concentrations returning to, and remaining within, the normal range for this species (Lunn, Dixson, Sandow & Fraser, 1990). With the protocol used in that study it was not possible to ascertain whether agonist treatment had resulted in any underlying effects on pituitary gonadotroph function.…”

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confidence: 97%

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Influence of the gonad on the degree of suppression induced by an LHRH agonist implant in the marmoset monkey

Lunn

Cowen²,

Morris³

et al. 1992

Journal of Endocrinology

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In a previous study pituitary-testicular function was shown to be maintained in a New World primate after the administration of an LHRH agonist implant. In the present study the mechanism of action of the same LHRH agonist (buserelin) on pituitary-gonadal function in the marmoset was investigated and a comparison made between the effects of treatment in three intact males, six adult cyclic females with regular ovulatory cycles, and six long-term ovariectomized animals. These were injected s.c. with an LHRH agonist implant (1.5 mg buserelin in a rod 0.5 cm long). In both the males and intact females, basal plasma LH concentrations were maintained within the normal range throughout the expected duration of agonist action (at least 3 months). Despite this, an absence of response to an LHRH challenge indicated that pituitary desensitization had occurred. In the intact females, ovulation was inhibited in five of six animals, plasma progesterone concentrations initially being maintained but subsequently remaining suppressed until 136 +/- 18 (S.E.M.) days after treatment. Responsiveness to administered LHRH returned prior to onset of return to ovarian cycles. In contrast, in ovariectomized marmosets, plasma LH was markedly suppressed to concentrations which were at or below the limit of detection of the assay and were therefore less than those observed in the buserelin-implanted intact animals. These results show that apparently normal pituitary-gonadal function in this species disguises an underlying pituitary desensitization to LHRH. This allows continuation of testosterone secretion in the male, but in the female ovulation is prevented, presumably as a result of failure of the desensitized pituitary to produce an LH surge.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…The marmoset (Callithrix jacchus) is an animal model for many reproductive biology studies and has been used extensively to study the effects of GnRH agonists and antagonists in vivo (Lunn et al 1990). The marmoset, unlike most other species, exhibits maintained secretion of luteinising hormone (LH) and testosterone after treatment with GnRH agonist implants, but not after GnRH antagonist treatment.…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterisation of the marmoset gonadotrophin releasing hormone receptor: Ser(140) of the DRS motif is substituted by Phe

Byrne

McGregor²,

Pl³

et al. 1999

Journal of Endocrinology

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In order to facilitate the understanding of gonadotrophinreleasing hormone (GnRH) agonist and antagonist action in the primate animal model, the marmoset GnRH receptor (GnRH-R) was cloned and characterised. It was shown to have 95% and 85% sequence identity with the human and rat GnRH-Rs, respectively, and, when transiently expressed in COS-7 cells, it exhibited high-affinity des-Gly 10 , ]-GnRH binding, with a K d value similar to those of both the rat and human forms, but with a greatly reduced B max value. The ED 50 for production of GnRH-induced total inositol phosphate (IP) for the marmoset GnRH-R was also similar to those of the rat and the human, but the maximal response compared with the rat receptor was markedly reduced. In all mammalian forms of the GnRH-R cloned to date, the conserved DRY region of G-protein-coupled receptors is substituted with DRS. The most interesting feature of the marmoset GnRH-R was the substitution of this motif with DRF. In order to investigate the DRS to DRF substitution, a Ser 140 Phe rat GnRH-R mutant was generated. The mutant had a K d value similar to that of the wild-type rat receptor, although the B max value was slightly lower, indicating that expression of functional mutant receptor at the cell surface was reduced. The ED 50 value for IP production was also similar to that of the wild-type receptor, with a reduction in maximal response. The level of internalisation for the rat wild-type and mutant GnRH-R constructs was also assessed and the Ser 140 Phe mutant was shown to have an increased rate of receptor internalisation, suggesting a role for this residue in regulating internalisation. These results show that the marmoset GnRH-R exhibits a substitution in the DRS motif and that this substitution may play a part in desensitisation and internalisation events.

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Pituitary-testicular function is suppressed by an LHRH antagonist but not by an LHRH agonist in the marmoset monkey

Cited by 26 publications

References 36 publications

Changes in endocrine profile and reproductive organs during puberty in the male marmoset monkey (Callithrix jacchus)

Changes in endocrine profile and reproductive organs during puberty in the male marmoset monkey (Callithrix jacchus)

Influence of the gonad on the degree of suppression induced by an LHRH agonist implant in the marmoset monkey

Isolation and characterisation of the marmoset gonadotrophin releasing hormone receptor: Ser(140) of the DRS motif is substituted by Phe

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