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Dissociated effect of buserelin on luteinizing hormone (LH) and alpha subunit in men

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Abstract

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.

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Authors and Affiliations

  1. Cattedra di Gerontologia e Geriatria, Università di Parma, Via Don Bosco 2, 43100, Parma, Italy

    Giorgio Valenti, L. Denti, A. Banchini, G. Ceresini & G. P. Ceda

  2. Reproductive Neuroendocrinology Section, Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC, 27709, USA

    W. C. Westel & A. Negro-Vilar

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  1. Giorgio Valenti
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Additional information

This direct gonadal effect may develop through a progressive desensitization of Leydig cells (5) or through an impairment of gonadal steroidogenesis due to inhibition of 17-hydroxylase and 17-20 a-desmolase activities (6). This direct inhibitory action

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Valenti, G., Denti, L., Banchini, A. et al. Dissociated effect of buserelin on luteinizing hormone (LH) and alpha subunit in men. J Endocrinol Invest 13, 459–467 (1990). https://doi.org/10.1007/BF03348599

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  • DOI: https://doi.org/10.1007/BF03348599

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