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ABSTRACT
Reproductive tissues, steroid hormone secretion, and sexual behaviour have been examined in five gilts, in each of which the right gonad was an ovotestis. Although from different females, these animals were sired by the same boar and each possessed an XX sex chromosome constitution as determined by karyotype analysis of blood cells. Despite variable amounts of testicular tissue in the ovotestis and unilateral development of a prominent epididymis, four of the animals had oestrous cycles of normal duration (20–22 days) and extended periods of standing oestrus (3–6 days). The fifth animal did not have detectable oestrous cycles but was extremely aggressive in the presence of a mature boar. Two of the gilts were mated, and there were small numbers of embryos in each uterine horn 23 and 26 days later. Removal of the ovary did not prompt compensatory hypertrophy in the ovarian portion of the ovotestis, nor did injection of pregnant mare serum gonadotrophin stimulate detectable follicular growth in ovarian tissue adjoining testicular tissue.
Concerning the aetiology of this intersex condition, the unilateral appearance of an ovotestis precludes any simple involvement of a translocated portion of the Y chromosome or systemic effects of unusual titres of the putative H–Y antigen. However, bearing in mind a predisposition to gonadal asymmetry in eutherian mammals, a case is advanced for apposition or incorporation of adrenocortical tissue in the right embryonic ovary. The resultant virilization of neighbouring reproductive tissues would stem from adrenocortical androgen synthesis.
J. Endocr. (1985) 106, 233–242
Isis Pharmaceuticals Inc., 1986 Rutherford Ave, Carlsbad, California 92008, USA
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia
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Isis Pharmaceuticals Inc., 1986 Rutherford Ave, Carlsbad, California 92008, USA
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia
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Isis Pharmaceuticals Inc., 1986 Rutherford Ave, Carlsbad, California 92008, USA
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia
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Isis Pharmaceuticals Inc., 1986 Rutherford Ave, Carlsbad, California 92008, USA
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia
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Isis Pharmaceuticals Inc., 1986 Rutherford Ave, Carlsbad, California 92008, USA
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia
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Isis Pharmaceuticals Inc., 1986 Rutherford Ave, Carlsbad, California 92008, USA
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia
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Isis Pharmaceuticals Inc., 1986 Rutherford Ave, Carlsbad, California 92008, USA
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia
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Isis Pharmaceuticals Inc., 1986 Rutherford Ave, Carlsbad, California 92008, USA
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia
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Isis Pharmaceuticals Inc., 1986 Rutherford Ave, Carlsbad, California 92008, USA
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia
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Isis Pharmaceuticals Inc., 1986 Rutherford Ave, Carlsbad, California 92008, USA
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia
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Isis Pharmaceuticals Inc., 1986 Rutherford Ave, Carlsbad, California 92008, USA
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia
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Diabetic retinopathy and acromegaly are diseases associated with excess action of GH and its effector IGF-I, and there is a need for improved therapies. We have designed an optimised 2′-O-(2-methoxyethyl)-modified phosphorothioate oligodeoxynucleotide, ATL 227446, and demonstrated its ability to suppress GH receptor mRNA in vitro. Subcutaneous injections of ATL 227446 reduced GH receptor mRNA levels, GH binding activity and serum IGF-I levels in mice after seven days of dosing. The reduction in serum IGF-I could be sustained for over ten weeks of dosing at therapeutically relevant levels, during which there was also a significant decrease in body weight gain in antisense-treated mice relative to saline and mismatch control-treated mice. The findings indicate that administration of an antisense oligonucleotide to the GH receptor may be applicable to human diseases in which suppression of GH action provides therapeutic benefit.
