Hypothyroidism In Male Rats Research Articles

Paternal treatment with kisspeptin improves offspring reproductive and metabolic changes caused by hypothyroidism in male rats

Paternal treatment with kisspeptin improves offspring reproductive and metabolic changes caused by hypothyroidism in male rats

Selenium protects against nesfatin-1 modulation of the hypothalamic-pituitary-testicular axis during hypothyroidism in male rats.

Normal gonadal function can be disrupted by hypothyroidism. Hypothyroidism disturbs testicular function directly and centrally by affecting the hypothalamic-pituitary-testicular axis with unclear mechanism. As nesfatin-1 neurons co-localized with TRH and GnRH neurons in the hypothalamus, it could play a role in centrally hypothyroidism induced testicular dysfunction. Selenium (Se), by affecting thyroid iodide supply, could relieve these disturbances. So, we aim to identify the role of nesfatin-1 as a link between testicular dysfunction and hypothyroidism through modulating the MAPK/ERK pathway while discussing the possible role of Se in alleviating hypothyroidism and associated testicular damage. Forty male rats were divided equally into: Control: distilled water, Se: Se orally, Propylthiouracil (PTU): PTU orally, PTU + Se: Se with PTU orally. Serum thyroid function, gonadal hormones, nesfatin-1, testicular redox status, sperm analysis, brain tissue GnRH, nucleobindin 2-derived polypeptide, pMAPK/ERK gene expression, histological changes and immunohistochemical expression of testicular proliferating cell antigen (PCNA) were done. PTU induced hypothyroidism and reduction of gonadal hormones which both were correlated with reduced nesfatin-1. There was testicular stress with reduced GnRH, NUCB2, pMAPK/ERK gene expression, and PCNA immunopositive cells. These parameters were reversed by Se. Nesfatin-1 could be the central link between hypothyroidism and disturbances of the hypothalamic pituitary testicular axis.

Spirulina platensis and Grape Seed Proanthocyanidin Extract ameliorates hepatic impairment in Carbimazole-induced hypothyroidism in male rats via caspase 8/Bcl-2 signaling pathway

Spirulina platensis and Grape Seed Proanthocyanidin Extract ameliorates hepatic impairment in Carbimazole-induced hypothyroidism in male rats via caspase 8/Bcl-2 signaling pathway

Do resident thyroid stem cells have a role in regeneration of hypophyseal thyroid axis after experimentally induced hypothyroidism in male rats? A histological and immunohistochemical study

Background Hypothyroidism is a common endocrine disorder characterized by a deficiency of thyroid hormones less than the normal levels. Recent research studies identified the presence of stem cells that act as a source of tissue regeneration within the thyroid gland. Aim To investigate the role of resident thyroid stem cells on the hypophyseal thyroid axis in experimentally induced hypothyroidism in male rats. Materials and methods A total of 30 healthy male rats were randomly divided into three groups. Group I was the control group). Group II was the hypothyroid group. It received carbimazole in a dose of 0.6 mg/kg dissolved in water to induce hypothyroidism. It was administered via an orogastric tube daily for 3 months. Group III was the withdrawal group. It included hypothyroid animals, as in group II, that were left without treatment for another month and then killed to assess hypothyroidism's recovery. The thyroid and pituitary glands were extracted from all groups and processed for histological and immunohistochemical analysis. Results The present study revealed that hypothyroidism caused marked histological changes in the pituitary–thyroid axis. Shrunken thyroid follicles with a significant increase in the epithelial height were seen. The colloid decreased in follicles or was completely absent in others. The follicular cells showed vacuolated cytoplasm. A significant increase in the number of parafollicular cells was observed. Thyrotrophs also appeared vacuolated with an increase in their number. Increase in the apoptotic cells and vascular endothelial growth factor-immunostained cells were observed. The withdrawal group showed moderate improvement in the architecture of the thyroid and pituitary glands. These results were confirmed by the morphometric and thyroid function test analysis. Conclusion The presence of resident thyroid stem cells led to moderate thyroid structure improvement but was not sufficient to restore the normal thyroid function.

Aframomum melegueta prevents the ejaculatory complications of propylthiouracil-induced hypothyroidism in sexually experienced male rats: Evidence from intravaginal and fictive ejaculations

ObjectiveHypothyroidism has been claimed to generate sexual dysfunctions such as ejaculatory disorders. Aframomum melegueta is an aphrodisiac plant with pro-ejaculatory properties. We investigated the protective effects of aqueous extract (AE) and methanolic extract (ME) of A. melegueta on the ejaculatory function of hypothyroid male rats. MethodsForty sexually experienced male rats were partitioned into 8 groups (5 rats per group) and treated for 28 d as follows: Group 1, Control; Group 2, propylthiouracil (PTU, 10 mg/kg) + distilled water (DW, 10 mL/kg); Group 3, PTU + 5% Tween 80 (10 mL/kg); Group 4, PTU + bromocriptine (6 mg/kg); Group 5, PTU + AE (20 mg/kg); Group 6, PTU + AE (100 mg/kg); Group 7, PTU + ME (20 mg/kg), and Group 8, PTU + ME (100 mg/kg). On days 0, 7, 14 and 28 of treatment, each male rat was paired with primed receptive female for measurement of ejaculatory latency time (ELT) and post-ejaculatory interval (PEI) for 1.5 h. On day 29, each male rat was urethane-anesthetized and the spinal cord was transected. Thereafter, following urethral/penile stimulations and intravenous injection of dopamine, contractions of the bulbospongiosus muscles and the intraseminal pressure were registered. After these recordings, blood was collected through the catheterization of abdominal artery and plasma was used for thyroid-stimulating hormone (TSH), prolactin and testosterone assays. ResultsPTU-induced hypothyroidism was characterized by a significant elevation (P < 0.001) of plasmatic TSH and prolactin levels, but a decline (P < 0.001) in plasmatic testosterone, compared to untreated group. ELT, PEI, contractions of the bulbospongiosus muscles and the intraseminal pressure were also altered by PTU treatment. On the contrary, A. melegueta extracts elevated testosterone (AE, 100 mg/kg, P < 0.01; ME, 100 mg/kg, P < 0.05) and decreased prolactin (AE, 100 mg/kg, P < 0.05; ME, 20 mg/kg, P < 0.05) levels, compared to corresponding controls. With regard to DW + PTU group, prolactin concentration was lowered (P < 0.05) in rats administered with bromocriptine. Treatment with A. melegueta extracts significantly prevented the lengthening of ELT (P < 0.05) and PEI (P < 0.001). Hypothyroid state also altered the fictive ejaculation by increasing the latency and decreasing the number and frequency of bulbospongiosus muscle contractions. There was also a decrease in the intraseminal pressure. These alterations were significantly (P < 0.05) alleviated in plant extract-treated groups. ConclusionThis study highlighted the ejaculatory disturbance of hypothyroidism in male rats and its prevention with A. melegueta extracts.

Hypothyroidism in Male Rats of Different Ages Exposed to Nitrate Polluted Drinking Water

The effect of nitrate pollution on the thyroid hormonal levels, body weight and other health indices was studied in male rats of different ages. The tested rats were divided into young (3 weeks old) and adult (12 weeks old) groups exposed to pollution via sodium nitrate (NaNO3) intake in drinking water in concentrations 100, 250, 550 mg/L daily for 4 months. The study revealed a dose dependent decrease in serum levels of thyroid hormones thyroxine (T4) and triiodothyronine (T3) accompanied by increased levels of thyroid stimulating hormone (TSH) in all nitrate exposed rats, indicating development of hypothyroidism. A significant reduction of the body weight gain was also recorded in the young animals at different nitrate doses, but only in the adults with the high dose. Meanwhile, a significantly elevated nitric oxide (NO) level in the serum and urine were noticed that confined to the young animals with medium (250 mg/ L) and high (550 mg/L) nitrate doses and the high dose adult animals. In addition, nitrate exposure resulted in a decreased serum concentrations of total proteins and protein fractions (albumin and globulin), accompanied by significant increases in the urea and creatinine levels in both serum and urine of the tested rats. This together with the above detected changes was found to exceed as the nitrate concentration increased and to be more pronounced in the young rats. Therefore, it can conclude that prolonged exposure to nitrate polluted drinking water is toxic to the thyroid hormonal activity and the other measured indices in both young and adult rats, but the young animals comprised the most age group susceptible to nitrate toxicity.

Effects of tri-iodothyronine on alternative splicing events in the coding region of cytochrome P450 aromatase in immature rat Sertoli cells.

Transient postnatal hypothyroidism in male rats induces a prolonged proliferation of immature Sertoli cells. This change in Sertoli cell replication at young ages is coincident with enhanced and prolonged aromatase activity that leads to a marked increase in the conversion of androgens into estrogens. Both events are drastically inhibited by tri-iodothyronine (T(3)) replacement either in vivo or in vitro. This study, after the immunolocalization of aromatase in cultured rat Sertoli cells, examined the effects elicited by T(3) on this enzyme, by simultaneously investigating three functional levels of aromatase: mRNA expression, protein content, and enzymatic activity. The immunolocalization of cytochrome P450 aromatase (P450 arom) was shown in the cytoplasm of cultured Sertoli cells from 15- and 21-day-old rats. Western blot analysis revealed an enhancement of aromatase protein content upon stimulation with N(6),2'-O-dibutyryladenosine-3':5'-cyclic monophosphate ((Bu)(2)cAMP) that was clearly down-regulated by T(3). The presence of a functional P450 arom protein in purified Sertoli cells was confirmed by the measurement of [(3)H]H(2)O released after incubation with [1 beta-(3)H]androst-4-ene-3,17-dione. With 100 nM T3, a decrease in both P450 arom mRNA levels and aromatase activity was observed. The aromatase enzymatic activity was strongly stimulated by (Bu)(2)cAMP and markedly down-regulated by T(3). In contrast, the strong increase in aromatase mRNA upon (Bu)(2)cAMP stimulation was apparently unaffected by T(3) administration. This paper shows how the identification of an altered transcript induced by T(3) coding for putative truncated and inactive aromatase protein might explain such a decrease in aromatase activity in T(3)-treated cells. On the basis of these results, it is concluded that at least two mechanisms could be involved in the down-regulatory effect of T(3) on aromatase activity in prepuberal Sertoli cells. The first mechanism is linked to a possible direct modulatory role for T(3) in the regulation of the aromatase promoter, whilst the second one is represented by the induction of altered transcripts coding for truncated and inactive aromatase proteins.

Effects of thyroid hormone (thyroxine) and testosterone on hepatic 11beta-hydroxysteroid dehydrogenase mRNA and activity in pubertal hypothyroid male rats.

To investigate the effects of thyroid hormone and testosterone on 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), we measured changes in hepatic 11beta-dehydrogenase activity and its mRNA levels in pubertal methimazole (MMI)-induced hypothyroid male rats following treatment with thyroxine ([T4] 50 microg/kg/d) or testosterone (250 microg/d) for 14 days. Hypothyroidism in male rats markedly reduced hepatic 11beta-HSD1 mRNA levels and serum testosterone concentrations (P < .01). Subcutaneous injection of T4 in the hypothyroid rats significantly (P < .01) increased hepatic 11beta-HSD1 mRNA to approximately normal levels and simultaneously increased serum testosterone levels. However, the same daily dose of T4 administered to castrated male hypothyroid rats for 14 days did not elevate hepatic 11beta-HSD1 activity. Treatment with testosterone for 14 days in castrated hypothyroid male rats and rats without gonadectomy significantly (P < .01) increased the enzyme activity without administration of T4. Variations in hepatic 11beta-HSD1 activity were demonstrated to be accompanied by changes in serum testosterone levels in the rats following alteration of the thyroid hormone state. These results suggest that the effect of T4 in increasing the subnormal 11beta-HSD1 gene expression in hypothyroid male rats is mediated by its ability to increase testosterone production in these rats, because in castrated hypothyroid rats, T4 does not elevate 11beta-HSD1 gene expression.

Hypothalamic nitric oxide synthase gene expression is regulated by thyroid hormones.

We investigated the effects of thyroid status on nitric oxide synthase (NOS) gene expression in the rat hypothalamic paraventricular (PVN) and supraoptic nuclei (SON). Propylthiouracil (PTU)-induced hypothyroidism in male rats produced a highly significant reduction in NOS gene transcripts in the PVN and SON, as assessed by quantitative in situ hybridization histochemistry with a specific oligodeoxynucleotide probe. The addition of T3 (40 micrograms/kg) to the PTU-containing diet completely prevented the reduction in NOS transcripts. Hyperthyroidism, induced by adding 160 micrograms/kg T3 to the food, more than doubled the prevalence of NOS transcripts in the PVN and SON after a similar time. Up-regulation of NOS gene transcripts induced by the osmotic stimulus of chronic salt loading was markedly attenuated by PTU-induced hypothyroidism. These results demonstrate a major effect of thyroid status on regulation of NOS gene expression in the hypothalamus.

Thyroid responses in rats fed diets formulated with Great Lakes coho salmon.

In earlier papers we reported thyroid hyperplasia and goiters together with clinical signs of hypothyroidism in male rats fed diets of Great Lakes coho salmon (OncorhYnchus kisutch) (SONSTEGARD & LEATHERLAND 1979a, LEATHERLAND & SONSTEGARD 1980). In these preliminary studies, the rats were fed a total fish diet without supplementation of any kind. The present paper reports on the effects of Great Lakes coho salmon on thyroid function in rats when the fish was given as part of a formulated diet together with rat chow, vitamin, mineral, and lipid supplementation. The study is a further attempt to assess the possible health hazards of using Great Lakes salmon for human consumption and an attempt to monitor the level of goitrogenic xenobiotics in the flesh of these fish.