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5α‐Reductase Type 2 and Androgen Receptor Expression in Gonadotropin Releasing Hormone GT1‐1 Cells
Author(s) -
Poletti A.,
Rampoldi A.,
Piccioni F.,
Volpi S.,
Simeoni S.,
Zanisi M.,
Martini L.
Publication year - 2001
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1046/j.1365-2826.2001.00635.x
Subject(s) - endocrinology , medicine , androgen receptor , gonadotropin , androgen , receptor , gonadotropin releasing hormone , hormone , chemistry , biology , luteinizing hormone , prostate cancer , cancer
Gonadal steroids are potent modulators of gonadotropin releasing hormone (GnRH) secretion, and androgen binding sites and 5α‐reductase activity have been found in the immortalized GnRH secreting cell line GT1‐1, suggesting the existence of a direct androgenic control of GnRH dynamics. Two isoforms of the 5α‐reductase have been cloned with very different biochemical/functional properties: 5α‐reductase type 1 (widely distributed in the body) and 5α‐reductase type 2 (confined in androgen target structures). We have analysed whether, in GT1‐1, androgen binding sites are linked to ‘classical’ androgen receptor, and which 5α‐reductase isoform is active. Reverse transcriptase‐polymerase chain reaction analysis showed that the mRNAs coding for androgen receptor and for the two 5α‐reductase isoforms are all expressed in GT1‐1 cells. However, the 5α‐reductase enzymatic reaction showed a peak of activity at a narrow pH around 5.5, the optimum for the 5α‐reductase type 2. The affinity for testosterone, of the enzyme present in GT1‐1 cells, was very similar to that observed for the recombinant type 2 isozyme expressed in yeasts. The data indicate that GT1‐1 cells (i) express a ‘classical’ androgen receptor and (ii) contain the 5α‐reductase type 2 isoform, a specific marker of androgen‐responsiveness.