Immunohistochemical demonstration of LH/CG receptors in non-neoplastic human adrenal cortex and adrenocortical tumors
Abstract
Introduction. Numerous data indicate that luteinizing hormone and/or chorionic gonadotropin (LH/CG) exert direct actions on the adrenal cortex and are involved in the adrenal pathology. However, the immunohistochemical studies on the expression of LH/CG receptors (LH/CGR) in the human adrenal cortex and in the adrenocortical tumors are scarce. Material and methods. Paraffin sections of samples of 6 human non-neoplastic adrenal cortex and 25 adrenocortical tumors were immunostained with anti-LH/CGR polyclonal antibody. Results. All zones of the human non-neoplastic adrenal cortex present a positive immunoreaction with anti-LH/CGR antibody showing the strongest reaction in cell membranes. The LH/CGR immunostaining in the vast majority of hormonally non-functioning adenomas and in all hormone-secreting adenomas does not differ from the non-neoplastic adrenal cortex. In contrast to non-neoplastic adrenal cortex and benign adenomas, in adrenocortical cancers the immunostaining with anti-LH/CGR antibody behaves differently. The immunopositive material is almost totally filling the cytoplasm of the cells but the immunopositivity of cell membranes is weak or lacking.
Conclusions. The data presented in our study show that the expression of LH/CGR in adrenocortical tumors is not ectopic but eutopic. The immunohistochemical examination of LH/CGR may be useful in the differentiation between benign and malignant lesions in the adrenal cortex. Moreover, the loss of membrane localization of LH/CGR in adrenocortical cancer suggests the alteration of receptors’ function.
Keywords: adrenal cortexadrenocortical adenomasadrenocortical cancerluteinizing hormone/chorionic gonadotropin receptor
References
- ROELS H. THE EFFECT OF SOME PITUITARY HORMONES ON VOLUME AND DNA CONTENT OF CELL NUCLEI OF THE ADRENAL CORTEX IN HYPOPHYSECTOMIZED-CASTRATED RATS. Exp Cell Res. 1963; 31: 407–415.
- Mikolajczyk H, Pawlikowski T. Histologic changes in the adrenal cortex of hypophysectomized-gonadectomized rats treated with gonadotrophins or adrenocorticotrophin. Endokrynol Pol. 1965; 16(4): 359–369.
- Mikolajczyk H. Possible synergic influence of ACTH and FSH on the adrenal cortex in hypophysectomized-gonadectomized rats. Nature. 1967; 213(5078): 806–807.
- Rosenbaum DM, Rasmussen SGF, Kobilka BK. The structure and function of G-protein-coupled receptors. Nature. 2009; 459(7245): 356–363.
- Pabon JE, Li X, Lei ZM, et al. Novel presence of luteinizing hormone/chorionic gonadotropin receptors in human adrenal glands. J Clin Endocrinol Metab. 1996; 81(6): 2397–2400.
- Nicolini G, Balzan S, Morelli L, et al. LH, progesterone, and TSH can stimulate aldosterone in vitro: a study on normal adrenal cortex and aldosterone producing adenoma. Horm Metab Res. 2014; 46(5): 318–321.
- Saner-Amigh K, Mayhew BA, Mantero F, et al. Elevated expression of luteinizing hormone receptor in aldosterone-producing adenomas. J Clin Endocrinol Metab. 2006; 91(3): 1136–1142.
- Zwermann O, Suttmann Y, Bidlingmaier M, et al. Screening for membrane hormone receptor expression in primary aldosteronism. Eur J Endocrinol. 2009; 160(3): 443–451.
- Bertagna X, Groussin L, Luton JP, et al. Aberrant receptor-mediated Cushing's syndrome. Horm Res. 2003; 59 Suppl 1: 99–103.
- Feelders RA, Lamberts SWJ, Hofland LJ, et al. Luteinizing hormone (LH)-responsive Cushing's syndrome: the demonstration of LH receptor messenger ribonucleic acid in hyperplastic adrenal cells, which respond to chorionic gonadotropin and serotonin agonists in vitro. J Clin Endocrinol Metab. 2003; 88(1): 230–237.
- Doroszko M, Chrusciel M, Stelmaszewska J, et al. GnRH antagonist treatment of malignant adrenocortical tumors. Endocr Relat Cancer. 2019; 26(1): 103–117.
- Rao C, Zhou XL, Lei ZM. Functional Luteinizing Hormone/Chorionic Gonadotropin Receptors in Human Adrenal Cortical H295R Cells. Biology of Reproduction. 2004; 71(2): 579–587.
- El Ghorayeb N, Bourdeau I, Lacroix A. Multiple aberrant hormone receptors in Cushing's syndrome. Eur J Endocrinol. 2015; 173(4): M45–M60.
- Lasley B, Conley A, Morrison J, et al. Identification of Immunoreactive Luteinizing Hormone Receptors in the Adrenal Cortex of the Female Rhesus Macaque. Reprod Sci. 2016; 23(4): 524–530.
- Pawlikowski M, Pisarek H, Kubiak R, et al. Immunohistochemical detection of FSH receptors in pituitary adenomas and adrenal tumors. Folia Histochem Cytobiol. 2012; 50(3): 325–330.
- Vuorenoja S, Rivero-Muller A, Kiiveri S, et al. Adrenocortical tumorigenesis, luteinizing hormone receptor and transcription factors GATA-4 and GATA-6. Mol Cell Endocrinol. 2007; 269(1-2): 38–45.
- Bernichtein S, Alevizaki M, Huhtaniemi I. Is the adrenal cortex a target for gonadotropins? Trends Endocrinol Metab. 2008; 19(7): 231–238.