Distribution of Labeled Retinyl Acetate and Retinoic Acid in Rat and Human Testes. A Possible Site of Retinyl Acetate Incorporation in Rat Testes

Ahluwalia, Balwant; Gambhir, Kanwal K.; Sekhon, H S

doi:10.1093/jn/105.4.467

Cited by 15 publications

(4 citation statements)

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“…0.1-0.2 mg/week retinol) (12). Ahluwalia et al (29) has found uptake of retinyl acetate by Sertoli cells, but there was no detectable uptake of radioactive labeled RA by the seminiferous tubules when it was given in the same amount as retinyl acetate. These findings may be related to the fact that Sertoli cells contain only small amounts of cellular retinoic acid-binding protein (CRABP), but high levels of cellular retinol-binding protein (CRBP) (17).…”

Section: Discussionmentioning

confidence: 99%

Retinoic Acid Is Able to Reinitiate Spermatogenesis in Vitamin A-Deficient Rats and High Replicate Doses Support the Full Development of Spermatogenic Cells

Pelt¹,

Rooij²

1991

Endocrinology

193

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The effect of various doses of retinoic acid (RA) on the seminiferous epithelium in vitamin A-deficient rats has been studied. Although it was generally thought that RA was not able to reinitiate spermatogenesis in vitamin A-deficient rats, one injection of 5 mg RA strongly stimulated the proliferative activity of A-spermatogonia within 24 h, as evidenced by a 7-fold increase in the number of bromodeoxyuridine-labeled A-spermatogonia. Ten days after RA administration, B-spermatogonia or preleptotene spermatocytes were seen in most of the seminiferous tubules. After 15 days, zygotene spermatocytes were present. Hence, RA is able to induce a massive and synchronized development of A-spermatogonia into spermatocytes. When RA was given once, combined with a RA-containing diet, only few of the zygotene spermatocytes present on day 15 were able to develop into pachytene spermatocytes, which did not develop into spermatids. In subsequent epithelial cycles new B-spermatogonia and spermatocytes were formed, although in lower numbers than during the first cycle after RA injection. When RA was given once a week, the formation of B-spermatogonia and preleptotene spermatocytes continued at a higher level. Also, more pachytene spermatocytes were formed, some of which were able to develop into spermatids. Finally, when RA was injected twice a week, even more pachytene spermatocytes and round spermatids were found after 36 days, and after 49 days elongated spermatids were found in all animals. It is concluded that RA, similar to retinol, is able to induce synchronous proliferation and differentiation of A-spermatogonia. When repeated injections are given, RA is able to support the full development of spermatogenic cells into elongated spermatids.

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Section: Discussionmentioning

confidence: 99%

Retinoic Acid Is Able to Reinitiate Spermatogenesis in Vitamin A-Deficient Rats and High Replicate Doses Support the Full Development of Spermatogenic Cells

Pelt¹,

Rooij²

1991

Endocrinology

193

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“…Knowledge of testicular retinoid metabolism is limited to analytical surveys of whole organ extracts (Ito et al, 1974;Napoli & McCormick, 1981;Bhat & Lacroix, 1983) and metabolic studies utilizing extracts obtained from testis injected with [3H]retinyl acetate (Chaudhary & Nelson, 1985). Evidence of the distribution of retinoids has been inferred from the histological examination of testicular tissue for labeled retinol and retinyl esters by autoradiography (Ahluwalia et al, 1975(Ahluwalia et al, , 1980Shakuntala et al, 1982) and by immunohistochemical analysis of CRBP and CRABP (Porter et al, 1985). Direct examination of metabolic events in individual testicular cell types is clearly required in order to elucidate the complex role the retinoids play in reproduction.…”

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confidence: 99%

Uptake and metabolism of retinol in cultured Sertoli cells: evidence for a kinetic model

Bishop¹,

Griswold²

1987

Biochemistry

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When cultured Sertoli cells derived from 20-day-old weanling rats were supplied [3H]retinol bound to serum retinol binding protein-transthyretin complex, [3H]retinol was rapidly incorporated and [3H]retinyl esters were synthesized. Within 28 h after administration, 83% of the labeled retinoids were accounted for as retinyl esters (64% as retinyl palmitate). Sertoli cells derived from vitamin A deficient rats and supplied [3H]retinol in culture under identical conditions likewise incorporated [3H]retinol and synthesized retinyl esters. In contrast to normal Sertoli cells, vitamin A deficient Sertoli cells eventually metabolized virtually all of the cellular [3H]retinol to retinyl esters. The primary metabolic fate of retinol administered to Sertoli cell cultures was the synthesis of retinyl esters under all conditions tested. However, administration of [3H]retinol bound to serum retinol binding protein gave metabolic profiles having a higher proportion of retinyl esters and lower proportions of unresolved polar material than administration of [3H]retinol alone. The kinetics of retinol uptake and intracellular retinyl ester synthesis in cultured Sertoli cells was complex. An initial, rapid phase of [3H]retinol incorporation lasting 30 min was followed by a slower rate of incorporation and a concomitant decrease in the intracellular concentration of [3H]retinol. During the time course the specific activity of [3H]retinyl palmitate eventually exceeded that of intracellular [3H]retinol. These observations suggest that two intracellular pools of retinol may exist in Sertoli cells.

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“…Based on uptake of administered radiolabeled RA, some tissues, such as the testes, pancreas and spleen, appear to possess a specific barrier for exposure to circulating ATRA, instead relying on synthesis of ATRA within the tissue [60–63]. Whether this functional barrier is due to RA metabolism or efflux transport is not known, but metabolism has been suggested to impair the access of RA to the testes [60]. Other tissues, such as the brain and the liver seem to be in equilibrium with blood, with 80–90% of the tissue RA pool being obtained from plasma [61].…”

Section: Regulation Of Retinoic Acid Homeostasis and Importance Ofmentioning

confidence: 99%

Therapeutic Potential of the Inhibition of the Retinoic Acid Hydroxylases CYP26A1 and CYP26B1 by Xenobiotics

Nelson¹,

Buttrick²,

Isoherranen³

2013

CTMC

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Retinoic acid (RA), the active metabolite of vitamin A, is an important endogenous signaling molecule regulating cell cycle and maintenance of epithelia. RA isomers are also used as drugs to treat various cancers and dermatological diseases. However, the therapeutic uses of RA isomers are limited due to side effects such as teratogenicity, and resistance to treatment emerging mainly from autoinduction of RA metabolism. To improve the therapeutic usefulness of retinoids, RA metabolism blocking agents (RAMBAs) have been developed. These inhibitors generally target the cytochrome P450 (CYP) enzymes because RA clearance is predominantly mediated by P450s. Since the initial identification of inhibitors of RA metabolism, CYP26 enzymes have been characterized as the main enzymes responsible for RA clearance. This makes CYP26 enzymes an attractive target for the development of novel therapeutics for cancer and dermatological conditions. The basic principle of development of CYP26 inhibitors is that endogenous RA concentrations will be increased in the presence of a CYP26 inhibitor, thus, potentiating the activity of endogenous RA in a cell-type specific manner. This will reduce side effects compared to administration of RA and allow for more targeted therapy. In clinical trials, inhibitors of RA metabolism have been effective in treatment of psoriasis and other dermatological conditions as well as in some cancers. However, no CYP26 inhibitor has yet been approved for clinical use. This review summarizes the history of development of RAMBAs, the clinical and preclinical studies with the various structural series and the available knowledge of structure activity relationships of CYP26 inhibitors.

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Distribution of Labeled Retinyl Acetate and Retinoic Acid in Rat and Human Testes. A Possible Site of Retinyl Acetate Incorporation in Rat Testes

Cited by 15 publications

References 0 publications

Retinoic Acid Is Able to Reinitiate Spermatogenesis in Vitamin A-Deficient Rats and High Replicate Doses Support the Full Development of Spermatogenic Cells

Retinoic Acid Is Able to Reinitiate Spermatogenesis in Vitamin A-Deficient Rats and High Replicate Doses Support the Full Development of Spermatogenic Cells

Uptake and metabolism of retinol in cultured Sertoli cells: evidence for a kinetic model

Therapeutic Potential of the Inhibition of the Retinoic Acid Hydroxylases CYP26A1 and CYP26B1 by Xenobiotics

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