Biomedical subjects

M M Aruldhas

Publications and source records attributed to M M Aruldhas.

At least 19 recordsLinked to original sources

PubMed2007

Effect of lycopene on insulin-like growth factor-I, IGF binding protein-3 and IGF type-I receptor in prostate cancer cells.

PURPOSE: 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 the 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 induces apoptosis. Hence, higher intake of lycopene can be associated with the lower risk of prostate cancer. However, the mechanism of action of lycopene in the prevention of prostate cancer is still unclear. The present study was carried out to study the effects of lycopene on the components of IGF system and apoptosis in androgen-independent prostate cancer cells (PC-3 cells). METHODS: PC-3 cells were treated with various concentrations of lycopene, (20, 40 and 60 microM) for 24, 48, 72 and 96 h. IGF-I, IGFBP-3 and IGF-I receptor (IGF-IR) levels in lycopene-treated cells were evaluated. Annexin V and propidium iodide (PI) binding studies were done to assess apoptosis. RESULTS: PC-3 cells treated with lycopene showed a significant decrease in cell proliferation. Lycopene, at a dose of 40 microM, significantly increased the level of IGFBP-3. Lycopene-induced apoptosis was confirmed by annexin V and PI binding. Lycopene-induced DNA fragmentation was absent after 24 h 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. CONCLUSION: The data obtained suggest that the components of the IGF system may act as a positive regulator of lycopene-induced apoptosis in PC-3 cells. Thus, the observed lycopene-induced biological effects and their associated mechanisms are encouraging and may lead to the development of a highly successful drug for the treatment of prostate cancer.

Annexin A5↗

PubMed2006

Effect of 17beta-estradiol on apoptosis, IGF system components and gelatinases A and B in prostate cancer cells (PC-3).

BACKGROUND: Previous studies have indicated that estrogen administration in the advanced stage of prostate cancer provide some benefits to the patients. Estrogen action was thought to be mediated via the blockade of the pituitary-testicular axis that effectively lowered the circulating levels of androgen and, thus, results in tumor regression; however, the effect of estrogens on prostate epithelial cells is still unclear. We investigated the effects of estradiol on insulin-like growth factor type I receptor (IGF-IR), IGF-binding protein 3 (IGFBP-3), IGFBP-4, and matrix metalloproteinase 2 (MMP-2) and MMP-9 in androgen-independent prostate cancer cells (PC-3). METHODS: The cells were treated with different concentrations of estradiol (1, 10 and 100 nmol/l) for different time periods (24, 48, 72 and 96 h). Cell proliferation was assessed using MTT assay, and IGFBP-3 and IGFBP-4 were assessed using immunoradiometric and enzyme immunoassays, respectively. MMP-2, MMP-9 and IGF-IR expression levels were analyzed using western-blot analysis, and MMP-2 and MMP-9 activities were analyzed using gelatin zymography. Apoptosis was confirmed by Annexin V-FITC and acridine orange and ethidium bromide staining methods. DNA fragmentation studies were also performed. RESULTS: Cell proliferation assay revealed that 10 and 100 nmol/l estradiol concentrations inhibit the proliferation of PC-3 cells when incubated for 48-96 h. The secretory levels of IGFBP-3 and IGFBP-4 were increased significantly. The western-blot results showed that estradiol is capable of decreasing the expression of MMP-2 and MMP-9 significantly. Gelatin zymography showed that activities of MMP-2 and MMP-9 are decreased in estradiol-treated cells. Estradiol-induced apoptosis was studied using annexin V-binding and propidium iodide influx. Estradiol also induced nuclear fragmentation in higher doses (100 nmol/l) in PC-3 cells. CONCLUSION: Inhibition of MMPs in cancer cells and increased levels of IGFBP-3 and IGFBP-4 associated with apoptosis may be one of the targets for anticancer function of estradiol. Estradiol inhibits the proliferation of prostate cancer cells by inducing apoptosis.

Apoptosis↗

PubMed2006

Effects of glucose and its modulation by insulin and estradiol on BMSC differentiation into osteoblastic lineages.

It is well known that diabetes affects bone in human and animal models, and leads to osteopenia and osteoporosis. Bone-mineral density and other biochemical markers of bone turnover are very much affected in people with diabetes. Reduced bone mass, occurring with increased frequency in diabetes mellitus, has been attributed to poor glycemic control, but the pathogenic mechanisms remain unknown. High concentrations of glucose (hyperglycemia) in diabetics leads to this complication. Very few in vitro studies using bone-cell lines have been carried out to address this problem. In this study, we examined the effects of different doses of glucose concentration (5.5, 16.5, and 49.4 mmol/L), alone, with insulin (0.6 microg/mL), or with 17beta-estradiol (E2) (10 nmol/L), on rat bone-marrow stromal cells (BMSCs) in the presence of an osteogenic medium. BMSC proliferation and alkaline phosphatase (ALP) were studied after 3 and 7 d of culture, respectively; the area stained for collagen and mineralized nodules was studied after 28 d of culture. With high concentrations of glucose, BMSC proliferation, ALP activity, the number of nodules formed, and the area stained for collagen were greatly reduced. Insulin treatment alone was able to increase [3H]-thymidine uptake or ALP activity, whereas both insulin and estradiol were able to increase the number of mineralized nodules and the area stained for collagen and mineralization. In conclusion, this study suggests that insulin and estradiol are able to contain the deleterious effect of high concentrations of glucose on BMSC-derived osteoblast proliferation and function.

Alkaline Phosphatase↗

PubMed2006

Effects of streptozotocin-induced diabetes mellitus on some bone turnover markers in the vertebrae of ovary-intact and ovariectomized adult rats.

Diabetes mellitus and estrogen deficit are known causes of osteopenia in animal models as well as in humans. In the present work, the combined effect of ovariectomy and diabetes was investigated. Diabetes was induced in ovary-intact and ovariectomized female Wistar rats with a single injection (50 mg/kg body weight, i.p.) of streptozotocin. The rats were administered insulin (I) daily or 17-beta estradiol (E2) on alternate days for a period of 35 days and sacrificed. Serum calcium (Ca2+), phosphorus (P), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), vertebral ALP, collagen, and glycosaminoglycans were estimated. The levels of serum Ca2+ and P increased in diabetic rats, but decreased after I or E2 treatments. Serum ALP and TRAP activity increased in the ovary-intact and ovariectomized diabetic rats. Vertebral ALP activity increased in ovariectomized diabetic rats, but decreased in diabetic rats, which were treated with I or E2. In the vertebrae, TRAP activity was elevated as a result of diabetes, but this was prevented by insulin or estradiol. Diabetes induced a decrease in total collagen in the vertebrae, while I or E2 treatment induced an increase. The levels of chondroitin sulphate and heparan sulphate decreased significantly in the vertebrae of both ovary-intact and ovariectomized diabetic rats, while hyaluronic acid increased. In conclusion, diabetes and ovariectomy each seem to affect the process of matrix formation and mineralization in the bone, and this is aggravated by the combination of diabetes and ovariectomy. The effects of I and E2 were similar, and both hormones reversed the changes brought about by diabetes.

Acid Phosphatase↗

PubMed2005

Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression.

Prostate cancer is the major health problem and the leading cause of male cancer death. Quercetin is a novel antitumor and antioxidant, whose molecular mechanism involved in cell cycle arrest in androgen independent prostate cancer cells remains unclear. In this study, we investigated the effects of quercetin on proliferation and cell cycle arrest by modulation of Cdc2/Cdk-1 protein in prostate cancer cells (PC-3). PC- 3 cells are human androgen independent cancer cells and were cultured with quercetin at concentrations of 50 and 100 microM for 24 h. Cell proliferation, apoptosis and cell cycle distribution were analyzed. Expression of Cdc2/Cdk-1, cyclin B1, cyclin A, p21/Cip1, pRb, pRb2/p130, Bcl-2, Bcl-X(L), Bax and caspase-3 proteins were studied with western blot analysis. Addition of quercetin led to substantial decrease in the expression of Cdc2/Cdk-1, cyclin B1 and phosphorylated pRb and increase in p21. Flowcytometric analysis showed that quercetin blocks G2-M transition, with significant induction of apoptosis. Apoptosis markers like Bcl-2 and Bcl-X(L) were significantly decreased and Bax and caspase-3 were increased. From this study, it was concluded that quercetin inhibits prostate cancer cell proliferation by altering the expression of cell cycle regulators and apoptotic proteins.

Antineoplastic Agents↗

PubMed2005

Antioxidant effect of ascorbic acid on PCB (Aroclor 1254) induced oxidative stress in hypothalamus of albino rats.

BACKGROUND: PCBs are one of the environmental toxicants and neurotoxic compounds which induce the production of free radicals leading to oxidative stress. Vitamin C is well known as an outstanding antioxidant. We determined the protective role of ascorbate on hypothalamic antioxidant system of Aroclor 1254 exposed rats. METHODS: The rats were injected Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days. One group of rats received vitamin C (100 mg/kg bw/day) orally simultaneously with Aroclor 1254 for 30 days. Twenty-four hours after last treatment, the animals were killed and hypothalamic region was separated from brain tissue. Enzymatic and non-enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and vitamin C were estimated. Hydrogen peroxide (H(2)O(2)), lipid peroxidation (LPO) and acetylcholine esterase (AchE) activity were determined. Serum gonadotropins such as luteinizing hormone (LH) and follicle stimulating hormone (FSH) were also assayed. RESULTS: Activities of SOD, CAT, GPx, GR, AchE and the concentration of vitamin C were decreased while an increase in H(2)O(2) and LPO were observed in hypothalamus of PCB treated animals. LH and FSH concentrations were also decreased in serum of PCB exposed animals. Vitamin C administration retrieved all the parameters significantly except serum hormonal profiles. CONCLUSION: PCB induces oxidative stress in hypothalamus by decreasing the activities of antioxidant enzymes, which can be protected by vitamin C treatment.

Acetylcholinesterase↗

PubMed2005

Effect of Aroclor 1254 on Sertoli cellular antioxidant system, androgen binding protein and lactate in adult rat in vitro.

Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental toxicants. Previous studies suggested that PCBs (Aroclor 1254) induce toxic effects including reproductive toxicity. The present study was designed to investigate the impact of Aroclor 1254 on Sertoli cellular function and antioxidant system of adult rat in vitro. Sertoli cells were isolated from adult rat testes and treated with various concentrations (10(-10) to 10(-7) M) of Aroclor 1254 for 6, 12 and 24 h. After the treatment period, cell viability was assessed and the Sertoli cellular antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), gamma-glutamyl transpeptidase (gamma-GT) and glutathione reductase (GR) and lipid peroxidation (LPO) were assayed. In addition, androgen binding protein (ABP) and lactate secretions were also quantified in Sertoli cell culture medium. Sertoli cellular viability and activity of antioxidant enzymes were significantly reduced in Aroclor 1254 (10(-10) to 10(-7) M) treatment for 6, 12 and 24 h whereas, the Sertoli cellular lipid peroxidation was significantly increased in a dose and duration dependent manner. In addition, ABP secretion diminished and lactate secretion was significantly elevated in the same manner. To conclude, the present study suggested that Aroclor 1254 disrupts Sertoli cellular metabolic functions such as ABP, lactate secretions and activity of antioxidant enzymes.

Androgen-Binding Protein↗

PubMed2005

Impact of polychlorinated biphenyl Aroclor 1254 on testicular antioxidant system in adult rats.

To clarify the reproductive toxicity of polychlorinated biphenyl compounds through determination of testicular lipid peroxidation, reactive oxygen species and enzymatic and non-enzymatic antioxidants in rats exposed to Aroclor 1254. Adult male rats were administered Aroclor 1254 at a dose of 2 mg/kg per day ip for 30 days. The rats were sacrificed 24 hours after last dosing and the serum and other tissues collected and processed for relevant determinations. The body weight and the weights of the testis, epididymis, ventral prostate and seminal vesicle and the serum testosterone and estradiol were significantly decreased in Aroclor 1254 treated rats. The testicular lipid peroxidation, hydrogen peroxide and hydroxyl radical were significantly elevated whereas, testicular antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and glutathione reductase (GR) were significantly decreased. The non-enzymatic antioxidants, vitamin C and vitamin E, were also decreased. These results suggest that Aroclor 1254 induces an increase in the lipid peroxidation, hydrogen peroxide and hydroxyl radical and diminish in the antioxidant defense system in rats, indicating that the free radical-dependent mechanism may play an important role in the testicular toxicity of polychlorinated biphenyls.

Animals↗

PubMed2004

Effects of Vitamin C and E on PCB (Aroclor 1254) induced oxidative stress, androgen binding protein and lactate in rat Sertoli cells.

The effect of Aroclor 1254 and the ameliorative effect of Vitamin C and E on Sertoli cell function were studied in adult male rats. The rats were administered Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days. One group of rats received Vitamin C (100 mg/kg bw/day) while the other group received Vitamin E (50 mg/kg bw/day) orally simultaneously with Aroclor 1254 for 30 days. Necropsy was performed at 24 h after the last injection. Sertoli cells were isolated for the estimation of enzymatic antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GST), and gamma-glutamyl transpeptidase (gamma-GT). Lipid peroxidation (LPO), hydrogen peroxide and hydroxyl radical were estimated. Sertoli cellular androgen binding protein (ABP) and lactate were also quantified. Whereas body weight, testis weight, relative weight of testis, ABP, lactate and specific activities of SOD, CAT, GPx, GR, GST, gamma-GT were all decreased, the levels of hydrogen peroxide, hydroxyl radical and LPO were significantly increased in the Sertoli cells of Aroclor 1254 treated rats. Simultaneous administration of Vitamin C or E restored these parameters to a normal range. Thus, the present study suggests that Aroclor 1254 exposure induces oxidative stress in rat Sertoli cells and furthermore that simultaneous administration of Vitamin C or E ameliorated these effects.

Androgen-Binding Protein↗

PubMed2004

Impact of polychlorinated biphenyl (Aroclor 1254) and vitamin C on antioxidant system of rat ventral prostate.

AIM: To evaluate the effect of polychlorinated biphenyls (PCB) and vitamin C on ventral prostatic antioxidant system in adult male rats. METHODS: A group of 20 adult male rats were administered ip Aroclor 1254 in corn oil at a dose of 2 mg x kg(-1) x day(-1) for 30 days. Ten control rats were administered only the vehicle. After 30 days the treated rats were divided at random into 2 sub-groups of 10 animals each. One sub-group received vitamin C at a dose of 500 mg x kg(-1) x day(-1) for 10 days. The other group was maintained as Aroclor 1254 control. Twenty-four hours after the last treatment the rats were killed by decapitation. Ventral prostatic homogenate was prepared and used for the estimation of enzymatic antioxidants, including superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) and hydrogen peroxide (H(2)O(2)), lipid peroxidation (LPO) and prostatic acid phosphatase. The serum levels of total T3, total T4, TSH, testosterone and estradiol were also assayed. RESULTS: The body weight and ventral prostatic weight were reduced in PCB treated rats. The activities of SOD, CAT, GST and acid phosphatase were decreased while the levels of H(2)O(2) and lipid peroxidation were increased in the ventral prostate of PCB treated rats. Administration of vitamin C restored these parameters. Serum levels of thyroid hormones, estradiol and testosterone were decreased in PCB treated animals. Administration of vitamin C restored the thyroid hormone levels. CONCLUSION: PCB induces oxidative stress and decreases the antioxidant enzymes in the ventral prostate of adult male rats; the effects could be reversed by the administration of vitamin C.

Acid Phosphatase↗

PubMed2003

Modulatory effect of estradiol and testosterone on the development of N-nitrosodiisopropanolamine induced thyroid tumors in female rats.

Both experimental and clinical research support the conclusion that thyroid tumors are sex dependent. Also, several studies have pointed out that the use of oral contraceptives is associated with a higher risk of thyroid tumor. Most of the existing reports suggest indirect effects of sex steroids on thyroid tumor growth in women. In this work, we present data to support the direct promoting effect of estradiol and testosterone on carcinogen-induced thyroid tumorigenesis. Thyroid tumors were induced in rats by a combination of N-nitrosodiisopropanolamine (DHPN) and phenobarbital (PB) treatment. Serum thyroid hormones, thyroid stimulating hormone (TSH), steroid hormones, thyroidal steroid concentration, androgen and estrogen receptors were quantified. Serum thyroid hormones and TSH suggested euthyroid status of the all experimental animals. Ovariectomy decreased the incidence of DHPN + PB induced thyroid tumor when compared with ovary intact rats and estradiol/testosterone supplementation increased the same. Thyroidal estradiol level and its nuclear receptors increased in the tumor tissue specifically. Testosterone supplementation to DHPN-treated ovariectomized rats specifically induced the development of malignant thyroid tumors. Addition of estradiol in vitro to thyrocytes induced a higher proliferation rate. Our data proves a direct promoting role of estrogen on carcinogen-induced thyroid tumor development.

Animals↗

PubMed2003

Effect of polychlorinated biphenyl, Aroclor 1254 on rat epididymis.

BACKGROUND & OBJECTIVES: Polychlorinated biphenyls (PCB), the synthetic chlorinated organic compounds, are known to decrease thyroid function, sperm count and fertility, and increase the risk of testicular cancer may cause serious effect on male reproduction. The objective of the present study was to study the effect of PCB, Aroclor 1254 on rat epididymal structure and function. METHODS: Adult male albino rats were treated ip with Aroclor 1254, 200 microg/kg body weight for 15 and 30 days. Serum levels of testosterone, estradiol, total triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) were measured by radioimmunoassay. The epididymal weight, sperm count, and caudal epididymal sialic acid, glyceryl phosphoryl choline (GPC) were also investigated. Histological studies were done on caput and caudal epididymal regions. RESULTS: Serum testosterone showed no change, but estradiol levels increased in 30 days treated animals, T3 and T4 levels decreased and TSH levels increased in both 15 and 30 days treated animals. Body weight, epididymal weight, sialic acid, GPC and sperm count were decreased only in 30 days Aroclor treated group. INTERPRETATION & CONCLUSION: The results suggested that Aroclor 1254 treatment for 15 and 30 days induced hypothyroidism in rats, but epididymal functions were altered only at 30 days treatment. The adverse effect of Aroclor 1254 (PCB) on epididymis might be due to indirect action through hormonal regulation.

Animals↗

PubMed2002

Impact of foetal-onset hypothyroidism on the epididymis of mature rats.

It is well established that congenital hypothyroidism leads to male infertility. However, there is a dearth of information on foetal-onset hypothyroidism-induced changes in the epididymis. With regard to transient hypothyroidism, the existing literature deals mainly with the testis. However, it is not known whether there is any corresponding alteration in epididymal morphology and physiology under such a condition. The present study is therefore aimed at understanding the impact of persistent and transient hypothyroidism on the concentration of epididymal sex steroids, as they play a vital role in maintaining the normal structure and function of the epididymis. Normal rats of 90 days of age served as controls (Group I). Hypothyroidism was induced by using pregnant/lactating mothers and post-weaning rats to 0.05% (w/v) methimazole (MMI) in the drinking water. Group II were subjected to persistent hypothyroidism from day 9 of post-coitum (pc) to 90 days. Group III rats were subjected to transient hypothyroidism from day 9 day pc to day 1 post-partum (pp), 21 pp or 35 pp (IIIa, b and c, respectively) and group IV rats were given simultaneous T3 supplementation (3 microg/100 g body wt./day i.m.) with MMI from day 9 pc to day 1 pp; 21 pp and 35 pp (Group IVa, b and c). Animals from all groups were killed on day 90 pp. Serum thyroid stimulating hormone (TSH) and thyroid hormones confirmed euthyroidism in group I, IIIa, b and c and IVa, b and c rats and hypothyroidism in group II rats. Caput and cauda epididymal concentration of testosterone, dihydrotestosterone (DHT), estradiol (E2) and androgen binding protein (ABP) markedly decreased in group II rats. While the concentration of testosterone, E2 and ABP increased in group III rats, that of DHT remained unaltered. However, group IV rats maintained normal concentration of the sex steroid and ABP. The activity of 5-alpha-reductase in the epididymis of all the groups followed the same trend as that of the concentration of epididymal DHT. From the present data it is evident that persistent hypothyroidism diminishes the bioavailability of androgens and oestrogens, while transient hypothyroidism enhances the same, indicating the importance of euthyroidism during foetal and neonatal period towards the maintenance of optimal hormonal status in the epididymis required for its maturation.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2002

Sex steroids regulate TSH-induced thyroid growth during sexual maturation in Wistar rats.

Sex steroids have been reported to influence thyroid pathogenesis in human and experimental animals. However, there is no much report on the effect of sex steroids in the growth of normal thyroid. The present study is an attempt to know TSH-induced thyroid growth during sexual maturation in Wistar rats. Wistar rats of day 1 to day 150 postpartum (pp) were used in the present study. Thyroid growth indices such as absolute and relative thyroid weights, concentration of DNA in the thyroid, mitotic index and numerical density of thyrocytes, hormonal profiles in the serum and thyroid tissue such as thyrotropin (TSH), thyroid hormones, testosterone and estradiol, and receptors for TSH, androgen and estrogen in the thyroid were estimated. A gender-specific shift in the pattern of serum TSH and TSH-R was observed during 30-45 days of postnatal life, the period at which steroidogenesis by testes or ovaries of rats are reactivated. Testosterone in males and estradiol in females modulate thyroid growth through TSH. It is concluded from the present study that changes in the sex steroid status between male and female rats have a definite influence on the pattern of thyroid growth and TSH.

Animals↗

PubMed2002

Adverse effects of neonatal hypothyroidism on Wistar rat spermatogenesis.

The effect of neonatal hypothyroidism on spermatogenesis was studied in Wistar rats of different age groups. Hypothyroidism was induced in newborn male rats from day one postpartum up to day 60 postpartum by daily administration of 0.05% methimazole (MMI) to the nursing mothers or directly through drinking water. The animals were killed at days 10, 15, 30, 40, and 60 postpartum, blood plasma was collected, and testes, epididymides, prostates, and seminal vesicles were separated and weighed. Testes were fixed in formalin for histological studies. Plasma testosterone (T), estradiol (E2), and sex hormone binding globulin (SHBG) were measured by radioimmunoassay. Hypothyroidism significantly reduced seminiferous tubule and lumen diameter. Control rats showed active spermatogenesis whereas in hypothyroid rats, the proliferation and differentiation of germ cells were arrested and their number was decreased. Plasma T, E2, and SHBG levels were significantly decreased at all ages for hypothyroid rats. The absolute weight of testes was decreased irrespective of age (except day 10 postpartum), however ventral, dorsolateral prostate, and epididymis weights were decreased at 30, 40, and 60 days postpartum. Coagulating gland weight was decreased in all age groups of hypothyroid rats. Hypothyroid rats of day 40 and 60 postpartum showed a decrease in absolute seminal vesicle weight. Relative testicular weights of hypothyroid rats decreased by postpartum day 15, 30, 40, and 60 whereas the opposite effect was observed by postpartum day 10. Relative organ weights were increased in epididymides (day 15 and 30 postpartum), seminal vesicles (day 30 and 40 postpartum), and dorsolateral prostates (day 15, 30, and 40 postpartum) and decreased in 10 and 60 day old hypothyroid rat. Ventral prostate relative weight was decreased in 40 and 60 day old rats. Th coagulating gland weight was decreased in 10, 15, and 60 days postpartum and an opposite effect was observed in 30 and 40 days hypothyroid rats. The present study clearly indicates that hypothyroidism adversely affects spermatogenesis; it also indicates that thyroid hormones are essential for normal spermatogenesis. Their effect may either be direct or indirect.

Aging↗

PubMed2001

Testosterone and estradiol modulate TSH-binding in the thyrocytes of Wistar rats: influence of age and sex.

Age and sex are important factors that influence thyroid pathophysiology. Though sex steroids are known to enhance thyrotropin (TSH) mRNA expression and incidence of thyroid tumours, there is no report on their effects on TSH action under normal physiological conditions. In the present study, the effects of testosterone (T) and estradiol (E2) on thyroidal TSH-receptor (TSH-R) concentration, and TSH-binding to thyrocytes (in vitro) were elucidated in immature and mature Wistar rats. Immature (10 days old) and adult (120 days old) rats of either sex were gonadectomized (GDX) and one group of GDX rats was treated with physiological doses of T and another with E2. Immature GDX rats were supplemented with the steroids for 10 days and adults were supplemented with the steroids for 30 days. While supplementation of steroids to immature rats was begun immediately after surgery, for adult rats it was started 10 days after gonadectomy. The rats were killed at the end of the experimental period. Gonadectomy significantly decreased serum TSH, and TSH-R concentration under in vivo condition and [125I]-TSH binding to thyrocytes under in vitro conditions. Supplementation of T to male and E2 to female GDX rats restored normality of the parameters. Thyrocytes of immature male rats challenged with linearly increasing doses of TSH or T (6.25-800 ng/ml) showed a dose-dependent increase in TSH-binding. However, thyrocytes of immature female rats challenged with T showed a gender-specific response. While there was a linear increase in TSH-binding in thyrocytes of males, a biphasic response was evident in thyrocytes of females. In the case of thyrocytes from adult rats, T induced a dose-dependent change in TSH-binding in males, which reached the peak in response to 12.5 ng T, and diminished thereafter. In contrast, E2 was inhibitory to TSH-binding to thyrocytes of adult male rats. On the other hand, E2 showed a clear gender-specific stimulation of TSH-binding in thyrocytes of females and an inhibition of the same in males. TSH and sex steroids upregulated TSH receptors in immature rats, whereas the effect was biphasic in adult rat thyrocytes. It is concluded from the present study that sex steroids modulate TSH-binding in rat thyrocytes, which may vary according to the age and sex of the animals.

Age Factors↗

PubMed2001

Prolactin and Leydig cells: biphasic effects of prolactin on LH-, T3- and GH-induced testosterone/oestradiol secretion by Leydig cells in pubertal rats.

The effect of rat prolactin (rPRL) on basal and LH-, GH- and T3-mediated testosterone and oestradiol secretion was studied in pubertal rat Leydig cells. Purified Leydig cells were cultured for 24 h at 37 degrees C in a medium containing 4% foetal calf serum (FCS). The medium was then replaced with fresh medium containing different concentrations of rPRL (5-400 ng/mL) for 48 h at 34 degrees C without FCS. rPRL increased testosterone secretion by Leydig cells at doses of 50-400 ng and maximum stimulation was observed at a dose of 200 ng. Oestradiol secretion was parallel to that of testosterone except at low doses (5-50 ng/mL). To assess the modulatory effect of rPRL on LH-, GH- and T3-induced Leydig cell testosterone and oestradiol secretion, minimum (50 ng) and maximum (200 ng) effective doses of rPRL were co-administered with LH (25/100 ng), GH (10/50 ng) and T3 (25/50 ng). Co-administration of rPRL (50/100 ng) with T3 (25/50 ng) decreased testosterone secretion. While co-administration of T3 (25 ng) decreased rPRL-induced oestradiol secretion, the latter was unaltered at a dose of 50 ng T3. A minimum effective dose of rPRL (50 ng) plus LH (25 ng) stimulated both testosterone and oestradiol secretion. While a maximum effective dose of rPRL (200 ng) did not alter LH (25 ng)-induced testosterone and oestradiol secretion, it inhibited testosterone secretion induced by 100 ng LH and increased oestradiol secretion. Both doses of rPRL (50, 200 ng) plus GH (10/50 ng) inhibited testosterone secretion when compared with testosterone secretion induced by either GH or PRL alone and stimulated oestradiol secretion. The present in vitro study indicates that rPRL stimulates both testosterone and oestradiol secretion by Leydig cells and that this effect can be modulated by LH, GH and T3.

Animals↗

PubMed2001

Differential effect of hyperthyroidism on rat epididymal glycosidases.

The impact of hyperthyroidism on epididymal glycosidases was studied in albino rats. Hyperthyroidism was induced in Wistar rats aged 30 days by daily injection of T4 (25 microg/100 g body weight/day intramuscularly) for 30 or 60 days; control rats were injected with vehicle (alkaline saline, pH 7.8). One set of hyperthyroid rats was reverted to euthyroid status by withdrawing T4 treatment after 30 days of hyperthyroidism. To asses the direct effect of thyroid hormone on epididymal hexosaminidases, caput, corpus and cauda tissues were stimulated with 25, 50 or 100 ng/mL T3 for 24 h, after an initial culture of 24 h. The activity of beta-glucosidase decreased in caput, corpus and cauda epididymis of hyperthyroid rats. beta-Galactosidase activity increased in the caput epididymis irrespective of the duration of hyperthyroidism. While a similar decrease occurred in the corpus and cauda epididymis in the 30 day hyperthyroid group, an opposite trend was observed in 60 day hyperthyroid rats. Caput beta-N-acetylglucosaminidase activities increased at both time points, whereas activity decreased in the corpus and cauda in 30 day, but increased in 60 day hyperthyroid rats. Hyperthyroidism consistently increased caput and corpus beta-N-acetylgalactosaminidase activity irrespective of the duration. Cauda epididymal beta-N-acetylgalactosaminidase activity was decreased in 30 day and increased in 60 day hyperthyroid rats. Hyperthyroidism induced changes in caput beta-galactosidase, beta-N-acetylgalactosaminidases, corpus beta-N-acetylglucosaminidase and cauda beta-N-acetylgalactosaminidase which were irreversible while the remaining actvities were brought back to normal when T4 treatment was withdrawn. In vitro studies showed that T3 stimulates epididymal hexosaminidases (beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase) irrespective of the dose. These data suggest that thyroid hormones have a specific and direct influence on glycosidases in specific regions of the epididymis.

Animals↗