Journal of Endocrinology and Reproduction

N. S. Venkatesh ¹, M. Kathiresh Kumar ¹, S. Sambavi ¹, N. Kalpana ¹, A. M. Sashi John ¹, J. Anbalagan ¹, R. Ilangovan ¹, M. M. Aruldhas ¹

Affiliations
1 Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600 113, IN

Abstract

Transient neonatal hypothyroidism is known to boost Sertoli cell (SC), Leydig cell (LC) and germ cell (GC) number at adult age. Existing reports attribute decreased steroidogenic potential of LCs to unaltered/decreased serum testosterone in such rats, despite a boost in the cell number. However, these studies have ignored the status of estradiol in such conditions. In this present study, we tested the hypothesis "transient neonatal-onset hypothyroidism may lead to a temporal shift in adult rat testicular steroidogenesis towards estradiol production". Hypothyroidism was induced in neonates by providing methimazole (MMI) in drinking water (0.05%) to lactating mothers and pups for a transient period from postnatal day 1 (PND 1) to PND 14 or from PND 1 to PND 29. After the experimental period, the pups were provided drinking water free of MMI and sacrificed on PND 91. Coeval rats without MMI exposure served as control. Radioimmunoassay revealed decreased serum titres of luteinizing hormone (LH), follicle stimulating hormone (FSH), growth hormone (GH) and prolactin (PRL); while serum testosterone remained unaltered, its level in testicular interstitial fluid (TIF) decreased. Between the two major metabolites of testosterone, 5α-dihydrotestosterone (DHT) concentration decreased in serum and TIF, whereas estradiol recorded a significant increase in both. Transient neonatal-onset hypothyroidism decreased 3β-hydroxy steroid dehydrogenase (3β-HSD) in LCs but augmented 17β-HSD activity. Radio-receptor assay revealed decreased concentration of LHR and ER in LCs of hypothyroid groups, whereas AR and PRLR increased. While aromatase activity decreased in LCs, it increased along with FSHR in SCs, when compared to control rats. The changes in LHR and FSHR levels and aromatase were consistent with the expression level of the respective genes. The present study supports the proposed hypothesis and suggests that transient neonatal-onset hypothyroidism-induced boost in estradiol in adult rat testis may be due to augmented expression and activity of aromatase, and FSHR content in SCs of these rats.

Keywords

Leydig Cells, Sertoli Cells, LHR, FSHR, Hypothyroidism.

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R. C. R. Udayakumar ¹, F. F. Antony ¹, J. Anbalagan ¹, R. Neelamohan ¹, A. J. Stanley ¹, M. M. Aruldhas ¹

Affiliations
1 Department of Endocrinology, Dr. ALM Post-Graduate Institute of Basic Medical Sciences, University of Madras Taramani Campus, Chennai - 600 113, IN

Abstract

Sertoli cells, the major site of intermediary metabolism in the testis, are the target for thyroid hormone action, though thyroid hormone receptors are present in Leydig cells also. We have earlier shown specific changes in basal and LH-induced steroidogenic activity in Leydig cells of adult rats with transient prepuberal - onset hypothyroidism. In this paper we report the response of Sertoli cell lipids and lipogenic enzymes in adult rats to prepuberal onset hypothyroidism. Hypothyroidism was induced in 30 day old rats by surgical thyroidectomy. After 60 days, one group of hypothyroid rats was allowed to attain euthyroidism by L-thyroxine (T₄) replacement therapy (intramuscular injection of 6μg T₄/100 g body weight for thirty days) and sacrificed. Sertoli cells were isolated by enzymatic dispersion and the concentration of various lipid fractions and the activities of lipogenic enzymes were assessed. Hypothyroidism increased Sertoli cell total lipids and total cholesterol, glycereides and phospholipids. Of the lipogenic enzymes, activities of glucose-6-phosphate dehydrogenase, 6-phospho gluconate dehydrogenase and malic enzyme decreased, whereas those of NADP+ isocitrate dehydrogenase, ATP-citrate lyase, fatty acid synthase and α - glycerophosphate dehydrogenase increased. T₄ replacement to thyroidectomized rats maintained normal levels of most of the parameters. The present study indicates that thyroid hormones have an inhibitory effect on Sertoli cell lipogenesis. It is suggested that accumulation of lipids in Sertoli cells may be one of the biochemical mechanisms underlying prepuberal-onset hypothyroidism-induced male infertility, which can be corrected with timely treatment of T₄ to maintain euthyroidism.

Keywords

Hypothyroidism, Lipids, Lipogenic Enzymes, Sertoli Cells, Testis, Thyroxine.

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A. M. J. Sashi ¹, N. S. Venkatesh ¹, P. Sekhar ¹, J. Anbalagan ¹, G. Vengatesh ¹, P. Govindarajulu ¹, M. M. Aruldhas ¹

Affiliations
1 Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, IN

Abstract

Hypogonadism and male infertility associated with congenital hypothyroidism are two important reproductive health problems. Studies emanated from our laboratory and a few others have established thyroid hormone as an important regulator of testicular development, growth, structure and function. Existing literature are centering around the effect of neonatal, prepuberal and puberal onset hypothyroidism on the testis of adult rats.

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P. Sekhar ¹, S. Subramanian ², N. S. Venkatesh ², A. M. J. Sashi ², N. Kalpana ², J. Anbalagan ², G. Vengatesh ², P. Govindarajulu ², M. A. Akbarsha ³, M. M. Aruldhas ²

Affiliations
1 Post Graduate Department of Zoology, Voorhees College, Vellore-632001, IN
2 Department of Endocrinology, University of Madras, Dr. ALM Post Graduate Institute of Basic Medical Sciences, Taramani Campus, Chennai-600113, IN
3 Department of Animal Science, Bharathidasan University, Tiruchirappalli-620024, IN

Abstract

Heavy metals and chemicals are known to cause male infertility. Chromium, an occupational heavy metal pollutant is a wellknown carcinogen with toxic effect on skin, lung and kidney. A few early reports point out the reproductive toxicity of chromium in experimental animals. An extensive study conducted in our laboratory in adult rats and monkeys established that altered prooxidant - antioxidant balance leading to free radical toxicity in the testis as the mechanism underlying the reproductive toxicity of chromium.

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A. M. J. Sashi ¹, N. S. Venkatesh ¹, G. Vengatesh ¹, P. Sekhar ¹, J. Anbalagan ¹, N. Kala ¹, P. Govindarajulu ¹, M. A. Akbarsha ², M. M. Aruldhas ¹

Affiliations
1 Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai-600113, IN
2 Department of Animal Science, Bharathidasan University, Tiruchirappalli-620024, IN

Abstract

Recent demonstration of thyroid hormone receptors (TR) in epididymis by our laboratory and that of Del Rio point out that epididymis may also be a target for the direct effect of T₃. Recent studies emanating from our laboratory have shown the importance of foetal-onset hypothyroidism on the growth, structure and function of the epididymis in adult rats. Since there are temporal difference in the foetal differentiation of hypothalamo-hypophyseal-testicular axis and the differentiation of testis and epididymis, it is hypothesized "Transient maternal hypothyroidism modifies specific cell types of the epididymis during pre-puberal, puberal and adult period in a temporal manner".

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P. Kanagaraj ¹, M. R. Vijayababu ¹, B. Ravisankar ¹, J. Anbalagan ¹, M. M. Aruldhas ¹, J. Arunakaran ¹

Affiliations
1 Department of Endocrinology, Dr ALM Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai - 600 113, IN

Abstract

Prostate cancer is the second most common cancer that leads to death in elderly men. The risk of prostate cancer prevalence is often associated with elevated level of insulin-like growth factor I (IGF-I) and decreased level of IGF-binding protein 3 (IGFBP-3). Lycopene, a carotenoid, reduces the proliferation of cancer cells and, thus, induces apoptosis. Hence, higher intake of lycopene can be associated with a lower risk of prostate cancer. However, the mechanism of action of lycopene in prostate cancer is still unclear. The present study was carried out to find the effects of lycopene on the components of IGF system and apoptosis in an androgen-independent prostate cancer cell (PC-3). PC-3 cells were treated with various concentrations of lycopene, 20, 40 and 60 μM, each for 24, 48, 72 and 96 h, IGF-1, IGFBP-3 and IGF-I receptor (IGF-IR) levels and indication of apoptosis were evaluated. The proliferation of lycopene-treated PC-3 cells decreased significantly. At a concentration of 40 μM lycopene treatment significantly increased the level of IGFBP-3. Lycopene-induced apoptosis was indicated in annexin V and PI binding. Lycopene-induced DNA fragmentation was not detectable after 24 h after the treatment whereas the same was observed after 48 h treatment. There was a significant decrease in the IGF-IR expression after the cells were treated with lycopene and IGF-I. The data obtained suggest that the components of the IGF system may act as a positive regulator for lycopene-induced apoptosis in PC-3 cells. The results obtained are encouraging and may lead to the development of lycopene as a potential therapy for prostate cancer.

Keywords

Lycopene, IGFBP-3, IGF-I, IGF-IR, Prostate Cancer.

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