This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Coutant, R. Articles by Limal, J.-M. Search for Related Content PubMed PubMed Citation Articles by Coutant, R. Articles by Limal, J.-M.

Macroorchidism due to Autonomous Hyperfunction of Sertoli Cells and G_s Gene Mutation: An Unusual Expression of McCune-Albright Syndrome in a Prepubertal Boy

Département de Pédiatrie, Centre Hospitalier Universitaire (R.C., S.R., J.M.L.), 49000 Angers, France; Laboratoire d’Hormonologie, INSERM, U-439, Centre Hospitalier de l’Universite de Montpellier (S.L., C.S.), 34090 Montpellier, France, Unité de Recherches sur l’Endocrinologie du Développement, INSERM, U-493, Ecole Normale Supérieure (R.R.), 92120 Montrouge, France, Centro de Investigaciones Endocrinológicas, Hospital de Niños R. Gutiérrez (R.R., M.V.), 1425 Buenos Aires, Argentina; and Laboratoire d’Hormonologie, Hôpital Saint Vincent de Paul (N.L.), 75014 Paris, France

Address all correspondence and requests for reprints to: Dr. Régis Coutant, Department of Pediatrics, University Hospital, 4 rue Larrey, 49000 Angers, France. E-mail: recoutant{at}chu-angers.fr

	Abstract

Top Abstract Introduction Materials and Methods Results Discussion References

 
We report an unusual observation of a 3.8-yr-old boy with McCune-Albright syndrome (MAS) associated with abnormal prepubertal testis enlargement and no sexual precocity. Physical examination showed café-au-lait skin lesions, enlarged testes, prepubertal sized penis, and no pubic or axillary hair. Skeletal radiography disclosed fibrous dysplasia. The serum testosterone level was 0.58 nmol/L and remained below 1.4 nmol/L during the 4-yr follow-up. By contrast, serum inhibin B and anti-Mullerian hormone concentrations were abnormally increased up to 255 pg/mL (childhood range, 35–180) and 792 pmol/L (childhood range, 309–566), respectively. The LH response to a GnRH test was in the prepubertal range, whereas the FSH response was blunted. This abnormal hormone concentration profile indicates autonomous hyperfunction of Sertoli cells, with no evidence of Leydig cell activation. Testicular histology showed tubules with marked Sertoli cell hyperplasia and very rare germinal cells, and interstitial tissue containing mesenchymal cells but no mature Leydig cells. DNA sequence analysis from bone and testis tissues detected the known activating mutation in MAS that results in replacement of Arg by His at codon 201 of the G_s protein. Other endocrine tests showed excessive GH secretion and moderate adrenal androgen hypersecretion.

These findings are consistent with the occurrence of an activating mutation of the G_s gene mainly expressed in Sertoli cells and weakly expressed or absent in Leydig cells. Abnormal prepubertal testicular enlargement extends the clinical spectrum of MAS, suggesting that determination of serum inhibin B and anti-Mullerian hormone should be considered in boys with this syndrome. This observation demonstrates the usefulness of detailed molecular and biological investigations in atypical cases of MAS.

	Introduction

Top Abstract Introduction Materials and Methods Results Discussion References

 
THE MCCUNE-ALBRIGHT syndrome (MAS), which occurs far more frequently in girls than in boys, is classically characterized by the triad of polyostotic fibrous dysplasia, café-au-lait skin lesions, and GnRH-independent sexual precocity (1, 2, 3, 4). Other various endocrinopathies have been described in this syndrome (3, 4, 5). Somatic gain of function mutations in the gene coding for the G_s protein have been found in affected tissues of patients with MAS, including the ovary, testis, adrenal gland, pituitary gland, thyroid gland, skin, and bone (3, 4, 5, 6, 7). G_s protein is implicated in the signaling pathway of numerous membrane-bound receptors, including receptors for several hormones. Substitution of Arg²⁰¹ by His or Cys decreases the guanosine triphosphatase activity of G_s, leading to constitutive activation of G_s protein. Somatic mosaicism of G_s protein results in an admixture of affected and normal cells and accounts for the variation in the site and degree of involvement of different tissues among patients with MAS (6).

Sexual precocity in MAS is due to activation of gonadotropin receptor signaling in the absence of interactions between gonadotropins and their receptors (6). Whereas precocious puberty is the common initial manifestation in girls, it has been reported in only 15% of affected boys (5). Subjects have enlarged testis in addition to signs of sexual precocity, and serum testosterone levels are in the pubertal range, contrasting with low secretion of LH and FSH (8, 9, 10, 11, 12, 13, 14).

We report an unusual clinical expression of MAS in a 3.8-yr-old boy presenting with abnormal prepubertal testicular enlargement but no sexual precocity. The hormonal, histological, and molecular investigations revealed testicular autonomous hyperfunction restricted to Sertoli cells with no activation of Leydig cells.

	Materials and Methods

Top Abstract Introduction Materials and Methods Results Discussion References

 
The subject and his family gave informed consent for this study.

Laboratory assays

Inhibin B was measured by means of a solid phase sandwich assay (Serotec, Oxford, UK) as previously described (15). Inhibin A exhibited 1% cross reactivity in the inhibin B assay. Intraassay precision was 7.4% and 4.2% at levels of 44 and 225 pg/mL, respectively. The sensitivity was 6 pg/mL. Reference values in boys aged 3–8 yr are 35–180 pg/mL. Anti-Mullerian hormone (AMH) was measured with a solid phase sandwich assay using reagents provided by Immunotech/Beckman Coulter, Inc. (Villepinte, France) (16, 17). There was no cross-reactivity of related proteins, including transforming growth factor-ß. Intraassay precision at 245 and 1106 pmol/L was 5.1% and 4.9%, respectively. The sensitivity was 0.7 pmol/L. Reference values in boys aged 4–7 yr were 309–566 pmol/L (17). RIAs were used to measure plasma concentrations of testosterone, dehydroepiandrosterone sulfate, cortisol, and aldosterone (Immunotech/Beckman Coulter, Inc.; Diagnostics Systems Laboratories, Inc., Webster TX). LH and FSH were measured by immunoradiometric assays (IRMAs; Immunotech/Beckman Coulter, Inc.; Coat-a-Count, Diagnostic Products, Los Angeles, CA) at baseline and after administration of 100 µg GnRH (gonadorelin, Ferring Pharmaceuticals Ltd., Gentilly, France). GH was measured by IRMA (CIS-Bio International, Gif-sur-Yvette, France). Total insulin-like growth factor I measurements were performed by IRMA after acid-ethanol extraction, PRL and hCG were measured by IRMA (Immunotech/Beckman Coulter, Inc.).

Identification of G_s gene mutation

A bone biopsy was performed at age 6.2 yr during surgery for a pathological femoral fracture. A testicular biopsy was obtained at age 7.5 yr by a surgical procedure; a three-cornered section, including albuginea, was made opposite the epididymis. The biopsy was divided into two fragments: a fragment consisting only of testicular parenchyma was snap-frozen for further molecular analysis, and the remaining tissue was used for histological studies. Enzymatic amplification was performed on DNA extracted from bone and testis tissues. A method previously described for selective enrichment of mosaic Arg²⁰¹ mutations was used, with minor modifications (18). Briefly, primer containing mismatch was used to generate a PCR product from the normal allele (normal codon 201) that is susceptible to EagI digestion, whereas that from the mutant allele (mutated codon 201) is resistant to digestion. Successive steps of PCR, enzymatic digestion, and nested PCR allowed selective enrichment of the product from the mutant allele. Experiments were limited to two steps of EagI treatment and nested PCR to reduce the risk of contamination. In addition, negative controls (no DNA) and normal DNA were included in all series of experiments. PCR products were purified and sequenced with the antisense primer using the ABI Prism Dye terminator sequencing kit (Perkin-Elmer Corp., Foster City, CA). Sequencing reactions were performed twice with two different PCR products.

Histological and immunocytochemical studies of testicular tissue

Testicular tissue was fixed in 4% paraformaldehyde in 0.1 mol/L phosphate buffer, dehydrated in a graded series of ethanols, and embedded in paraffin; 5-µm sections were cut and processed for routine hematoxylin-eosin staining. Immunocytochemistry was performed using the antigen retrieval technique by microwaves, as previously described (19), for AMH and inhibin ß_B-subunit. Antigen retrieval was not necessary for the detection of 3ß-hydroxysteroid dehydrogenase.

	Results

Top Abstract Introduction Materials and Methods Results Discussion References

 
Case report

A boy aged 3 yr, 10 months was admitted to our clinic because of right hip pain and alteration of gait. Physical examination revealed several café-au-lait spots on the back. The volume of the right testis was 9 mL, and that of the left was 7 mL. Contrasting with the pubertal volume of testes, the penis was infantile in size (4.5 x 1.5 cm), and there was no pubic or axillary hair. The height was 108 cm (+1.7 SD score), and growth velocity was 9 cm/yr (+2.7 SD score). There was no familial history of precocious puberty. Skeletal radiography showed numerous cystic areas of rarefaction in iliac and femoral bones, and thickening and expansion of the base of the skull. Bone age was 5 yr. A presumptive diagnosis of MAS was made.

Initial hormonal evaluation showed a prepubertal serum testosterone level of 0.58 nmol/L (Table 1). After the iv administration of GnRH, the peak serum LH level was in the prepubertal range, whereas the peak FSH level was blunted. By contrast, serum inhibin B was increased to 242 pg/mL, a pubertal level indicating Sertoli cell activation. Serum hCG was not detectable.

Growth rate was accelerated, and serum insulin-like growth factor I was abnormally elevated (Table 1). Excessive GH secretion was diagnosed, as high serum GH levels failed to decrease after an oral glucose tolerance test. The child received somatostatin analogs from the age of 6.6 yr.

Moderate adrenal hyperfunction was diagnosed as the serum dehydroepiandrosterone sulfate concentration was increased, with normal levels of cortisol and aldosterone (Table 1). The PRL concentration and serum TSH and free T₄ levels were in the normal range. Pituitary magnetic resonance imaging and adrenal computed tomography scan were normal.

Molecular study

Bone and testicular biopsies were performed, and DNA was extracted from the tissue specimens. Sequencing showed the presence of a guanine to adenine transversion leading to an Arg-His substitution at position 201 (Fig. 1) in bone and testis tissues. Both normal and mutant sequences of the G_s gene were present, indicating a somatic mutation and thus a mosaicism of normal and abnormal cells as observed in MAS. Due to the enrichment method used, evaluation and comparison of the amounts of mutant and wild-type DNAs were not applicable.

View larger version (21K): [in this window] [in a new window]   Figure 1. Partial chromatograms of exon 8 of the Gs gene showing the somatic R201H mutation in DNAs extracted from bone (left panel) and testis (right panel).

Testicular histology showed a majority of seminiferous tubules with slightly increased diameter, but no lumen, filled with hyperplastic Sertoli cells; germ cell number was significantly reduced. The basement membrane was enlarged, and the number of peritubular cell layers was increased. The interstitial tissue contained mesenchymal cells, but showed no Leydig cell maturation (Fig. 2A). The immunocytochemical study showed a homogeneously positive reaction in Sertoli cells for inhibin ß_B-subunit (Fig. 2B) and AMH (not shown). To probe an eventual steroidogenic activation of interstitial cells, we performed immunocytochemistry for enzyme 3ß-hydroxysteroid dehydrogenase; no positive reaction was observed. A positive reaction was observed in the Leydig cells from a section of pubertal testis taken from our tissue library and used as a control (not shown).

View larger version (72K): [in this window] [in a new window]   Figure 2. Histological and immunocytochemical study of testicular tissue. Bar, 50 µm. A, Sample representing the features of testicular tissue observed in 42 of 50 slides analyzed in this study. Seminiferous tubules show no lumen and are filled with Sertoli cells, the basement membrane (BM) is enlarged, and only interstitial cells (IC) with mesenchymal or fibroblastic appearance are seen in the interstitial tissue (hematoxylin-eosin stain). B, Immunohistochemistry for inhibin ßB-subunit shows an intense reaction in the cytoplasm of Sertoli cells.

	Discussion

Top Abstract Introduction Materials and Methods Results Discussion References

Only a dozen cases of sexual precocity in boys with MAS have been reported to date (8, 9, 10, 11, 12, 13, 14). Subjects had enlarged testes and penis in addition to premature pubic hair. Serum testosterone levels were in the pubertal range, whereas the responses of gonadotropins to GnRH were weak (8). Testicular histology showed seminiferous tubules lined by Sertoli cells and germ cells, whereas mesenchymal cells underwent maturation to Leydig cells (8, 14). The full process of spermatogenesis has been described in patients as young as 6 yr (8). These hormonal data and testicular findings appeared similar to those in boys with familial testotoxicosis and indicated LH receptor signaling pathway activation (14). Molecular studies performed on testis tissue in some cases revealed the expected mutation of the G_s gene in the specimens (6, 7, 13). One report, although labeled as precocious pubertal development, showed many similarities with the present case (12). The 6.5-yr-old affected boy had enlarged testes, contrasting with infantile penis and no pubic hair. Serum testosterone level and LH and FSH responses to GnRH were in the prepubertal range. Testicular histology showed mature tubules exhibiting spermatogenesis and interstitial tissue containing rare Leydig cells. Although inhibin B and AMH were not measured, prevailing Sertoli cell activation was likely.

The boy had tall stature, accelerated growth rate and advanced bone age. In the absence of circulating testosterone in the pubertal range, these features were probably explained by the excessive GH secretion and the abnormally increased adrenal androgen concentration. Pituitary and adrenal involvement has been previously reported in MAS (3, 4, 5, 6, 7, 11, 12).

Several explanations may account for the restriction of testicular autonomous hyperfunction to Sertoli cells in the present observation. One possibility is that somatic mutation of the G_s gene was present in Sertoli cells but not in Leydig cells (6). Although the mutation is believed to occur early in development of the embryo, the origin of Sertoli and Leydig cells is controversial, and recent reports in mouse indicated that the two populations show somewhat different ontogenies (20, 21). Alternatively, imprinting of the G_s gene, which has been hypothesized from studies on pseudohypoparathyroidism type I (22, 23, 24), may lead to cell-specific expression of the mutated gene; the allele encoding the activated G_s protein in our patient may be expressed in Sertoli cells, but not in Leydig cells. Another explanation arises from mouse models showing that overexpression of AMH exerts an inhibitory effect on Leydig cell maturation and function (25, 26). In our patient, strong expression of the activating mutation in Sertoli cells produced high levels of AMH, which may have counteracted the effect of weak expression of the mutation in Leydig cells.

Testicular histology was abnormal in this patient. The seminiferous tubules were filled with hyperplastic Sertoli cells, but germ cell number was reduced. The interstitial tissue contained mesenchymal cells, but there was no Leydig cell maturation. This is in sharp contrast with testicular findings in boys with MAS and sexual precocity. Whereas potent Leydig cell activation results in germinal cell maturation, isolated Sertoli cell activation may be detrimental for germinal cell maintenance.

In conclusion, we described a new endocrinopathy in MAS: abnormal testicular enlargement with no sexual precocity resulted from autonomous testicular hyperfunction restricted to Sertoli cell with no activation of Leydig cell. Determination of serum inhibin B and AMH in addition to testosterone and gonadotropins should be considered in boys with MAS to characterize potential testicular involvement. This observation demonstrates the usefulness of detailed molecular and biological investigations in atypical cases of MAS.

	Acknowledgments

 
We acknowledge L. Coupris and F. Laumonier, who kindly performed testis and bone biopsy.

	Footnotes

 
¹ Established researcher with the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, Argentina) supported by PICT97 05-064 (ANPCyT, Argentina) and invited professor at the Ecole Normale Supérieure, Département de Biologie, Montrouge, France (supported by Procedure PAST of the French Ministry of Education and Research).

Received July 21, 2000.

Revised November 10, 2000.

Revised December 6, 2000.

Accepted December 12, 2000.

	References

Top Abstract Introduction Materials and Methods Results Discussion References

 

1. Albright F, Butler A, Hampton A, Smith P. 1937 Syndrome characterized by osteitis fibrosa disseminata, areas of pigmentation and endocrine dysfunction, with precocious puberty in females. N Engl J Med. 216:727–746.
2. McCune D, Bruch H. 1937 Osteodystrophia fibrosa. Report of a case in which the condition was combined with precocious puberty, pathologic pigmentation of the skin, and hyperthyroidism, with a review of the literature. Am J Dis Child. 54:806–848.
3. Collins MT, Shenker A. 1999 McCune-Albright syndrome: new insights. Curr Opin Endocrinol Diabetes. 6:119–125.
4. Levine MA. 1999 Clinical implications of genetic defects in G proteins: oncogenic mutations in G_s as the molecular basis for the McCune-Albright syndrome. Arch Med Res. 30:522–531.[CrossRef][Medline]
5. Ringel MD, Schwindinger WF, Levine MA. 1996 Clinical implications of genetic defects in G proteins. The molecular basis of McCune-Albright syndrome and Albright hereditary osteodystrophy. Medicine. 75:171–184.[Medline]
6. Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM. 1991 Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med. 325:1688–1695.[Abstract]
7. Shenker A, Weinstein LS, Moran A, et al. 1993 Severe endocrine and nonendocrine manifestations of the McCune-Albright syndrome associated with activating mutations of stimulatory G protein GS. J Pediatr. 123:509–518.[CrossRef][Medline]
8. Majzoub JA, Scully RE. 1993 Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 7–1993. A six-year-old boy with multiple bone lesions, repeated fractures, and sexual precocity. N Engl J Med. 328:496–502.[Free Full Text]
9. Benedict PH. 1966 Sex precocity and polyostotic fibrous dysplasia: report of a case in a boy with testicular biopsy. Am J Dis Child. 111:426–429.[Medline]
10. Nitzan M, Laron Z, Pertzelan A, Scharf A. 1973 McCune-Albright syndrome with sexual precocity in a boy. Helv Paediatr Acta. 28:61–65.[Medline]
11. Lightner ES, Penny R, Frasier SD. 1975 Growth hormone excess and sexual precocity in polyostotic fibrous dysplasia (McCune-Albright syndrome): evidence for abnormal hypothalamic function. J Pediatr. 87:922–927.[CrossRef][Medline]
12. Giovanelli G, Bernasconi S, Banchini G. 1978 Mc-Cune-Albright syndrome in a male child. A clinical and endocrinologic enigma. J Pediatr. 92:220–226.[CrossRef][Medline]
13. Weinstein LS, Shenker A, Spiegel AM. Activating G protein mutations are present in the majority of patients with McCune-Albright syndrome (MAS) [Abstract]. 74th Annual Meet of The Endocrine Soc. 1992.
14. Grumbach MM, Stynne DM. 1998 Puberty: ontogeny, neuroendocrinology, physiology, and disorders. In: Wilson JD, Foster DW, Kronenberg HM, Larsen PR, eds. Williams textbook of endocrinology. ed. 9. WB Saunders Company; 1509–1625.
15. Lahlou N, Chabbert-Buffet N, Christin-Maitre S, Le Nestour E, Roger M, Bouchard P. 1999 Main inhibitor of follicle stimulating hormone in the luteal-follicular transition: inhibin A, oestradiol, or inhibin B? Hum Reprod. 14:1190–1193.[Abstract/Free Full Text]
16. Rey R, Lordereau-Richard I, Carel JC, et al. 1993 Anti-Mullerian hormone and testosterone serum levels are inversely related during normal and precocious pubertal development. J Clin Endocrinol Metab. 77:1220–1226.[Abstract]
17. Rey R, Belville C, Nihoul-Fékété C, et al. 1999 Evaluation of gonadal function in 107 intersex patients by means of serum anti-Mullerian hormone measurement. J Clin Endocrinol Metab. 84:627–631.[Abstract/Free Full Text]
18. Candeliere GA, Roughley PJ, Glorieux FH. 1997 Polymerase chain reaction-based technique for the selective enrichment and analysis of mosaic arg201 mutations in G_s from patients with fibrous dysplasia of bone. Bone. 21:201–206.[Medline]
19. Rey R, Al-Attar L, Louis F, et al. 1996 Testicular dysgenesis does not affect expression of anti-Müllerian hormone by Sertoli cells in pre-meiotic seminiferous tubules. Am J Pathol. 148:1689–1698.[Abstract]
20. Karl J, Capel B. 1998 Sertoli cells of the mouse testis originate from the coelomic epithelium. Dev Biol. 203:323–333.[CrossRef][Medline]
21. Martineau J, Nordqvist K, Tilmann C, Lovell-Badge R, Capel B. 1997 Male-specific cell migration into the developing gonad. Curr Biol. 7:958–968.[CrossRef][Medline]
22. Hayward BE, Kamiya M, Strain L, et al. 1998 The human GNAS1 gene is imprinted and encodes distinct paternally and biallelically expressed G proteins. Proc Natl Acad Sci USA. 95:10038–10043.[Abstract/Free Full Text]
23. Yu S, Yu D, Lee E, et al. 1998 Variable and tissue-specific hormone resistance in heterotrimeric G_s protein ()-subunit (G_s()) knockout mice is due to tissue-specific imprinting of the G_s() gene. Proc Natl Acad Sci USA. 95:8715–8720.[Abstract/Free Full Text]
24. Farfel Z, Bourne HR, Iiri T. 1999 The expanding spectrum of G protein diseases. N Engl J Med. 340:1012–1020.[Free Full Text]
25. Behringer RR, Cate LL, Froelick GJ, Palmiter RD, Brinster RL. 1990 Abnormal sexual development in transgenic mice chronically expressing Müllerian inhibiting substance. Nature. 345:167–170.[CrossRef][Medline]
26. Racine C, Rey R, Forest MG, et al. 1998 Receptors for anti-Müllerian hormone on Leydig cells are responsible for its effects on steroidogenesis and cell differentiation. Proc Natl Acad Sci USA. 95:594–599.[Abstract/Free Full Text]

This article has been cited by other articles:

				F. De Luca, V. Mitchell, M. Wasniewska, T. Arrigo, M. F. Messina, M. Valenzise, L. de Sanctis, and N. Lahlou Regulation of spermatogenesis in McCune-Albright syndrome: lessons from a 15-year follow-up. Eur. J. Endocrinol., June 1, 2008; 158(6): 921 - 927. [Abstract] [Full Text] [PDF]

				R. Coutant, D. Mallet, N. Lahlou, N. Bouhours-Nouet, A. Guichet, L. Coupris, A. Croue, and Y. Morel Heterozygous Mutation of Steroidogenic Factor-1 in 46,XY Subjects May Mimic Partial Androgen Insensitivity Syndrome J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 2868 - 2873. [Abstract] [Full Text] [PDF]

				R. A. Rey, M. Venara, R. Coutant, J.-B. Trabut, S. Rouleau, N. Lahlou, C. Sultan, J.-M. Limal, J.-Y. Picard, and S. Lumbroso Unexpected mosaicism of R201H-GNAS1 mutant-bearing cells in the testes underlie macro-orchidism without sexual precocity in McCune-Albright syndrome Hum. Mol. Genet., December 15, 2006; 15(24): 3538 - 3543. [Abstract] [Full Text] [PDF]

				N. Kalfa, A. Ecochard, C. Patte, P. Duvillard, F. Audran, C. Pienkowski, E. Thibaud, R. Brauner, C. Lecointre, D. Plantaz, et al. Activating Mutations of the Stimulatory G Protein in Juvenile Ovarian Granulosa Cell Tumors: A New Prognostic Factor? J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1842 - 1847. [Abstract] [Full Text] [PDF]

				M. M. Grumbach A Window of Opportunity: The Diagnosis of Gonadotropin Deficiency in the Male Infant J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 3122 - 3127. [Abstract] [Full Text] [PDF]

				S. Lumbroso, F. Paris, and C. Sultan Activating Gs{alpha} Mutations: Analysis of 113 Patients with Signs of McCune-Albright Syndrome--A European Collaborative Study J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2107 - 2113. [Abstract] [Full Text] [PDF]

				S. Ramaswamy, G. R. Marshall, C. R. Pohl, R. L. Friedman, and T. M. Plant Inhibitory and Stimulatory Regulation of Testicular Inhibin B Secretion by Luteinizing Hormone and Follicle-Stimulating Hormone, Respectively, in the Rhesus Monkey (Macaca mulatta) Endocrinology, April 1, 2003; 144(4): 1175 - 1185. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Coutant, R. Articles by Limal, J.-M. Search for Related Content PubMed PubMed Citation Articles by Coutant, R. Articles by Limal, J.-M.