Presence of Cortisol-Binding Protein in the Lens

Ono, Shigeru; Hirano, Hiroko; Obara, Kazuo

doi:10.1159/000266198

Cited by 20 publications

(8 citation statements)

References 2 publications

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“…The present study has demonstrated for the first time that sulphate and glucuronide conjugation of cortisol occurs in the lens as well as in other tissues, and recently the authors have shown the presence of cortisol-binding protein in the rat lens using a gel filtration technique and cortisol-4-14C [Ono et al, 1971], We found that there were two modes of inactivation of cortisol in the lens after it was absorbed, i.e., sulphate or glucuronide conjugation or cor tisol-binding by protein. The fact that steroid conjugation exists in the lens indicates one of the metabolic pathways for adrenocortical steroids admin istered either orally or locally with therapeutic purposes as an anti-inflam matory therapy in ophthalmology, and it is suggested that a decrease in conjugation of steroid in the lens may play some role in the onset of steroid cataracts because unbound with sulphate or glucuronide, the steroid becomes active, which is mainly inhibitory on the protein turnover in the lens.…”

Section: Resultssupporting

confidence: 58%

Study on the Conjugation of Cortisol in the Lens

Ono¹,

Hirano²,

Obara³

1972

Ophthalmic Res

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Sulphate and glucuronide conjugation of cortisol in the normal human, cataractous, bovine, rabbit and rat lens in vitro have been investigated using a cortisol-4–¹⁴C. The authors have verified the presence of sulphate and glucuronide conjugation of cortisol in the lens. There are species differences in conjugation of steroid in the lens. Conjugation in the human lens was found to be more active than that in other animals. Sulphate conjugation of cortisol in the cataractous lens was less than that in a normal human lens, whereas no change was found in glucuronide conjugation. These results have demonstrated that the lens is one of the organswhich conjugate the steroid hormone actively.

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Section: Resultssupporting

confidence: 58%

Study on the Conjugation of Cortisol in the Lens

Ono¹,

Hirano²,

Obara³

1972

Ophthalmic Res

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“…Its presence in the neuroretina is reminiscent of the situation in the brain where growth, development, differentiation and neonatal imprinting are some of the functions assigned to cortical hormones in the nervous tissue [22], Such action may be coordinated by glucocorticoid hormones acting via their respective receptors in the retina [12,13], although the cytochemical localization of the glucocorticoid receptor has never been ascertained. Some of these possibilities can be investigated in Müller cell cultures from rat retina now being developed in our laboratory.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, we investigated the possi ble presence of the MCR in the eye, particularly because ocular tissues possess the receptor for glucocorticoids [12,13] and respond to light by changes in sodium concentra tion [14,15], The data reported here show that the MCR is present in both the epithelial and neuronal cells of the eye. Therefore, ocular tissues form an interesting new tar get to study the mechanism of action of mineralotropic hormones.…”

Section: Introductionmentioning

confidence: 99%

Immunochemical Demonstration of the Mineralocorticoid Receptor in Ocular Tissues

Mirshahi

Sedighian

et al. 1997

Neuroendocrinology

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We studied the presence of the mineralocorticoid receptor (MCR) in the eye with the aid of a number of immunochemical techniques. Immunoblotting with a polyclonal antibody, directed against the rat renal MCR, revealed a single band of about 102 kD in extracts prepared from whole bovine or rat retina similar to that observed in cytosol from the kidney and myocardium from these species. Isolated cells of the bovine retinal pigment epithelium (RPE) similarly exhibited a 98- to 102-kD band in Western blots developed with the aid of anti-MCR antiserum. The 98- to 102-kD band was also obtained following autoradiography of RPE cytosol irradiated in the presence of ³H-R 5020. This fluorographic pattern was abolished when RU 26752, an antagonist specific to the MCR, was allowed to compete with radiolabelled promegestone. The MCR-³H-RU 26752 complex in RPE cytosol underwent heat activation, as judged by binding to DNA cellusose, and could also be precipitated by anti-MCR IgG. In primary cultures, the proliferation of the RPE cells was inhibited by the two MCR-specific antagonists RU 26752 and ZK 91587. The loss of the MCR-specific immunofluorescence in RPE cells after only 3 passages in culture was associated with refractoriness to the inhibitory effect of both of these spironolactones. Immunohistochemistry, using MCR-specific antiserum, revealed strong fluorescence in specific areas of the rat eye. In the retina, immunopositivity was observed in Müller cells, external and internal limiting membranes, the vitreous base lining and in the pigment epithelium. Epithelial cells of the ciliary body, iris and cornea also exhibited strong MCR-specific immunofluorescence. Thus, both the epithelial and the nonepithelial compartments of the ocular tissues form interesting new targets to delineate the mechanism of action of mineralotropic hormones.

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“…Glucocoticoid-binding proteins in the lens have been described (5,6), but the precise biochemical mechanism involved in cataract formation has not been found. We recently have demonstrated that steroids possessing a ketol moiety can react with protein amino groups to form stable covalent adducts (7).…”

Section: Introductionmentioning

confidence: 99%

Nonenzymatic addition of glucocorticoids to lens proteins in steroid-induced cataracts.

Manabe¹,

Bucala²,

Cerami³

1984

J. Clin. Invest.

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A bt~stract. A frequent manifestation of longterm glucocorticoid administration is the occurrence of posterior subcapsular cataracts. The molecular basis for this effect has not yet been elucidated. The addition of prednisolone to the rat lens in culture results in a timeand concentration-dependent lens opacification that correlates with the formation of covalent prednisolone-lens protein adducts. Prednisolone adduct formation was analyzed by [3H]prednisolone incorporation and by immunoprecipitation with antiserum specific for proteins modified by the nonenzymatic addition of prednisolone.In the rat lens, these adducts were localized in both the water-soluble and urea-soluble lens protein fractions. Gel electrophoresis and fluorography revealed that the most extensively modified proteins were two crystallins subunits. Lens proteins from 33 normal and cataractous human lenses were fractionated and analyzed for the presence of prednisolone-protein adducts by competitive radioimmunoassay. Adducts were detected only in those samples derived from glucocorticoid-induced cataractous lenses. We conclude that elevated glucocorticoid levels lead to the formation of glucocorticoid-lens protein adducts both in vitro and in vivo. Lens protein modification by glucocorticoids may lead to sufficient biochemical or structural alterations so as to result in cataract formation. The ability of glucocorticoids to form adducts with proteins in vivo also may play a role in some of the other toxic manifestations of long-term glucocorticoid therapy.

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Presence of Cortisol-Binding Protein in the Lens

Cited by 20 publications

References 2 publications

Study on the Conjugation of Cortisol in the Lens

Study on the Conjugation of Cortisol in the Lens

Immunochemical Demonstration of the Mineralocorticoid Receptor in Ocular Tissues

Nonenzymatic addition of glucocorticoids to lens proteins in steroid-induced cataracts.

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