Dissociated effect of buserelin on luteinizing hormone (LH) and alpha subunit in men
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Chronic treatment with LHRH analogs is known to depress testosterone (T) values to castration levels. In contrast to results from animal experiments, studies in humans indicate that a pituitary-dependent mechanism predominates in the suppression of plasma T. However, this reduction in T levels may occur when LH values are within or below the normal range. One explanation for this result has been that while absolute values of LH in serum may not change, the bioactivity of LH is reduced. The present study has been performed to determine whether this discrepancy between LH and T values is obscured by the hypersecretion of the α-subunit which is devoid of any biological activity but crossreacts in most RIAs with LH. Following 2 days of blood collection to establish basal serum hormone levels, six men with prostatic cancer were treated with the LHRH agonist, Buserelin (500 μg sc, daily injection) for 15 days. The most significant endocrine responses at the end of this treatment were as follows: 1) T levels were depressed to the castration range; 2) no change was seen in the LH values with a conventional RIA procedure which crossreacted with the α-subunit; 3) a significant decrease was found in the LH values evaluated with an immunoradiometric (IRMA) method, which shows no cross-reactivity with the α-subunit; 4) there was a significant increase in the α-subunit levels; and 5) serum FSH levels were significantly decreased. In addition, when the chromatographic profiles of immunoreactive LH and α-subunit were compared from a patient at the beginning and at the end of the study, there was a shift in the elution position of the LH molecule but no change in the elution profile of the α-subunit. On the basis of these results, it appears that the pituitary LH secretion is depressed by chronic treatment with Buserelin and this reduction is responsible for the suppression of T. In addition, it appears that Buserelin therapy may bring about an alteration in the molecular form of LH which is secreted into blood.
Taken together, these findings demostrate that the pituitary is the major site of action of Buserelin and that the discrepancy between the LH and T levels and between LH bioactivity and immunoreactivity values may be attributed both to the crossreactivity of the α-subunit in the LH RIA and to some change in the molecular form of LH which is secreted into the blood.
Key-wordsBuserelin alpha-subunit LH
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- 1.Mann D.R., Gould K.G., Collins D.C. Influence of continuous gonadotropin — releasing hormone (GnRH)agonist treatment on luteinizing hormone and testosterone secretion, the response to GnRH, and the testicular response to human chorionic gonadotropin in male Rhesus monkeys. J. Clin. Endocrinol. Metab. 58: 262, 1984.PubMedCrossRefGoogle Scholar
- 2.MannD.R., Smith M.M., Gould K.G., Collins D.C. Effect of gonadotropin-releasing hormone agonist on luteinizing hormohe and testosterone secretion and testicular histology in male Rhesus monkeys. Fertil. Steril. 43: 115, 1985Google Scholar
- 3.Sandow J., Jerabek-Sandow G., Knauss B., Schmidt-Gollwitzer M. Pharmacokinetics and metabolism of LHRH agonists, clinical aspects. In: Labrie F., Belanger A., Dupont A., (Eds.), LHRH and its analogs. Excerpta Medica, Amsterdam, 1984, p. 123.Google Scholar
- 8.Schaison G., Brailly S., Vuagnat P., Bouchard P., Milgrom E. Absence of a direct inhibitory effect of the gonadotropin-releasing hormone (GnRH) agonist D-Ser(TBU)6, des-Gly-NH10 2 GnRH Ethylamide (Buserelin) on testicular steroidogenesis in men. J. Clin.Endocrinol. Metab. 58: 885, 1984.PubMedCrossRefGoogle Scholar
- 9.Roman S.H., Goldstein M., Kourides I.A., Comite F., Bardin C.W., Krieger D.T. The luteinizing hormone-releasing hormone (LHRH) agonist (D-Trp6- Pro9-NET) LHRH increased rather than lowered LH and a-subunit levels in a patient with a LH-secreting pituitary tumor. J. Clin. Endocrinol. Metab. 58: 313, 1984.PubMedCrossRefGoogle Scholar
- 11.Schurmeyer T.H., Knuth U.A., Freischem C.W., Akhtar F.B., Nieschlag E. Suppression of pituitary and testicular function in normal men by constant gonadotropin-releasing hormone agonist infusion. J. Clin. Endocrinol. Metab. 59: 9, 1984.Google Scholar
- 22.Valenti G., Ceda G.P., Denti L., Cavalieri S., Dotti C. Studio delle interferenze dovute alia presenza della catena alfa in diversi sistemi di dosaggio delle gonadotropine. The Lig Quart (Ed. Ital.) 5: 300, 1986.Google Scholar
- 25.Dotti C., Ceda G.P., Denti L., Cavalieri S., Borasi G., Valenti G. Cross reactions in radiommunoassay: a mathematical model for correcting assay results, as exemplified by eliminating the interference of intact thyrotropin in an assay of its beta subunit. Clin. Chem. 33: 658, 1987.PubMedGoogle Scholar
- 26.Winer BJ Statical principles in experimental design. McGraw-Hill, New York, 1971.Google Scholar
- 27.Lahlou N., Roger M., Chaussain J.L., Feinstein M.C., Sultan. C., Toublanc J.E., Schally. A.V., Scholler R. Gonadotropin and a-subunit secretion during long term pituitary suppression by D-Trp — luteinizing hormone-releasing hormone microcapsules as treatment of precocious puberty. J. Clin. Endocrinol. Metab. 65: 946, 1987.PubMedCrossRefGoogle Scholar
- 28.Meldrum D.R., Tsao Z., Monroe S.E., Braunstein G.D., Sladek J., Lu J.K.H., Vale W., Rivier J., Judd HI., Chang R.J. Stimulation of LH fragments with reduced bioactivity following GnRH agonist administration in women. Endocrinology 115: 755, 1984.Google Scholar
- 36.Haisenleder D.J., Khoury S., Zmeili S.M., Papavasilou S., Ortolano G.A., Dee C., Duncan J.A., Marshall J.C. The frequency of gonadotropin-releasing hormone secretion regulates expression of α — and luteinizing hormone β-subunit messenger ribonucleic acids in male rats. Mol. Endocrinol. 1: 834, 1987.PubMedCrossRefGoogle Scholar
- 40.Strollo F., Harlin J., Hernandez-Montes H., Robertson D.M., Zaidi A. A., Diczfalousy E. Qualitative and quantitative differences in the isoelectrofocusing profile of biologically active lutropin in the blood of normally menstruating and postmenopausal women. Acta Endocrinol. (Copenh). 97: 166, 1981.PubMedGoogle Scholar
- 41.Green E.D., Baenzinger J.U. Asparagine-linked oligosaccharides on lutropin, follitropin and thyrotropin. J. Biol. Chem. 253: 36, 1988.Google Scholar