This Article Full Text (PDF) Submit a related Letter to the Editor 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 AXELROD, L. Articles by KLIMAN, B. Search for Related Content PubMed PubMed Citation Articles by AXELROD, L. Articles by KLIMAN, B.

Hypogonadism in a Male with Immunologically Active, Biologically Inactive Luteinizing Hormone: An Exception to a Venerable Rule^*

Diabetes and Endocrine Units of the Medical Services, Massachusetts General Hospital, and the Department of Medicine, Harvard Medical School Boston, Massachusetts 02114

Address requests for reprints to: Dr. Axelrod, Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts 02114.

A male patient, the product of a consanguineous mating, had normal primary sex characteristics but failed to enter puberty spontaneously. The plasma total testosterone level was low (30-81 ng/100 ml), the plasma immunoreactive LH level was elevated, and the bioassayable urine gonadotropin excretion rate was increased in the rat ovarian weight assay and the mouse uterine weight assay. Although these findings suggested a primary gonadal defect, he responded normally to a physiological dose of human LH, with a rise of the plasma total testosterone level to 430 ng/100 ml. Thus, the patient's Leydig cells responded to exogenous human LH but not to endogenous LH. The Leydig cells also responded normally to graded single doses of exogenous human LH and hCG, providing evidence against either a subtle abnormality in testicular responsiveness or a circulating LH antagonist. In fact, the patient developed secondary sex characteristics in response to chronic treatment with hCG, confirming the normal testicular responsiveness to exogenous gonadotropins. After administration of LRH, the immunoreactive plasma LH level rose markedly, but the immunoreactive plasma FSH level and the plasma testosterone level did not change. The testicular biopsy was consistent with the diagnosis of LH deficiency, and the karyotype was normal. Three normally developed maternal uncles with a history of infertility were also products of a consanguineous mating, and one had a subnormal plasma testosterone level.

These findings suggest that this syndrome is attributable to the presence of an abnormal LH, which is biologically inert in the affected patients but biologically active in rodents. The defect appears to be inherited. (J Clin Endocrinol Metab 48: 279, 1979)

^* This work was supported in part by Grant AM-04501 from the USPHS, NIH.

Received April 27, 1978.

This article has been cited by other articles:

				H. Valdes-Socin, R. Salvi, A. Thiry, A. F. Daly, F. P. Pralong, R. Gaillard, and A. Beckers Testicular Effects of Isolated Luteinizing Hormone Deficiency and Reversal by Long-Term Human Chorionic Gonadotropin Treatment J. Clin. Endocrinol. Metab., January 1, 2009; 94(1): 3 - 4. [Full Text] [PDF]

				H. Valdes-Socin, R. Salvi, A. F. Daly, R. C. Gaillard, P. Quatresooz, P.-M. Tebeu, F. P. Pralong, and A. Beckers Hypogonadism in a Patient with a Mutation in the Luteinizing Hormone Beta-Subunit Gene N. Engl. J. Med., December 16, 2004; 351(25): 2619 - 2625. [Abstract] [Full Text] [PDF]

				A. P. N. Themmen and I. T. Huhtaniemi Mutations of Gonadotropins and Gonadotropin Receptors: Elucidating the Physiology and Pathophysiology of Pituitary-Gonadal Function Endocr. Rev., October 1, 2000; 21(5): 551 - 583. [Abstract] [Full Text]

				S.-B. Hu, L. Johnson, P. C. Roche, and H. T. Keutmann A Functional Determinant in Human Luteinizing Hormone and Chorionic Gonadotropin: Differential Effect of Mutations about {beta}-GLN-54 Endocrinology, April 1, 1997; 138(4): 1627 - 1633. [Abstract] [Full Text] [PDF]

				R. J. POLLET and G. S. LEVEY Principles of Membrane Receptor Physiology and Their Application to Clinical Medicine Ann Intern Med, May 1, 1980; 92(5): 663 - 680. [Abstract] [PDF]