Thyroid hormone and leptin in the testis.

Leptin is primarily expressed in white adipose tissue; however, it is expressed in the hypothalamus and reproductive tissues as well. Leptin acts by activating the leptin receptors (Ob-Rs). Additionally, the regulation of several neuroendocrine and reproductive functions, including the inhibition of glucocorticoids and enhancement of thyroxine and sex hormone concentrations in human beings and mice are leptin functions. It has been suggested that thyroid hormones (TH) could directly regulate leptin expression. Additionally, hypothyroidism compromises the intracellular integration of leptin signaling specifically in the arcuate nucleus. Two TH receptor isoforms are expressed in the testis, TRa and TRb, with TRa being the predominant one that is present in all stages of development. The effects of TH involve the proliferation and differentiation of Sertoli and Leydig cells during development, spermatogenesis, and steroidogenesis. In this context, TH disorders are associated with sexual dysfunction. An endocrine and/or direct paracrine effect of leptin on the gonads inhibits testosterone production in Leydig cells. Further studies are necessary to clarify the effects of both hormones in the testis during hypothyroidism. The goal of this review is to highlight the current knowledge regarding leptin and TH in the testis.

The effects of liraglutide on male fertility: a case report.

Liraglutide is an agonist of the glucagon-like peptide I receptor, and is commonly recommended as a treatment for obesity and type 2 diabetes mellitus. Adverse effects related to liraglutide include acute pancreatitis and polyarthritis. No studies, however, have reported an adverse effect of liraglutide on male reproduction. This case report shows a deleterious effect of liraglutide on male reproductive function.

Perinatal malnutrition programs gene expression of leptin receptors isoforms in testis and prostate of adult rats.

The aim of this paper was to evaluate if maternal malnutrition during lactation programs the expression of leptin receptor isoforms in the testes and prostate ventral lobe of adult rats. At delivery, Wistar rats were separated into 3 groups: control group (C) with free access to a standard laboratory diet containing 22% protein; protein-energy restricted group (PER) with free access to an isoenergy and protein-restricted diet containing 8% protein; and energy-restricted group (ER) receiving standard laboratory diet in restricted quantities, which were calculated according to the mean ingestion of the PER group. All animals were sacrificed at 90 days of age. Both PER and ER groups presented low body weight from the first days after birth, however, while the ER group reached the control weight around day 80, the body weight of PER group was significantly lower compared to controls until the day the animals were killed. In relation to tissue weight, only the relative testis weight of the ER group presented an alteration compared to the control group (p<0.03). There was also no alteration in the leptin serum levels among the groups. The main leptin receptors isoforms, OBRa and OBRb were significantly increased in the testis (OBRa: C=0.71±0.10; PER=1.14±0.17; ER=1.92±0.70, p<0.0007, OBRb: C=0.87±0.04; PER=1.20±0.05; ER=1.44±0.17, p<0.001) and prostate (OBRa: C=0.70±0.18; PER=1.30±0.14; ER=1.65±0.22, p<0.014, OBRb: C=0.77±0.14; PER=1.16±0.04; ER=1.30±0.13, p<0.027) of both malnourished groups. However, the testis OBRc (C=1.52±0.06; PER=1.35±0.23; ER=3.50±0.72, p<0.023) and OBRf (C=1.31±0.12; PER=1.66±0.27; ER=3.47±0.55, p<0.009) and prostate OBRc (C=0.48±0.13; ER=1.18±0.34, p<0.01) and OBRf (C=0.73±0.15; PER=0.99±0.11; ER=1.83±0.30, p<0.016) isoforms were significantly increased only in the ER group. The results presented here show for the first time that both testis and prostate leptin receptor isoforms gene expression are programmed by perinatal malnutrition. These data further stress the importance of monitoring maternal and neonatal status, as well as other pathophysiological situations, to combat the appearance of long-term diseases.

Molecular and morphometric analysis of the rat ventral prostate injected with leptin.

The aim of this study was to evaluate the effect of leptin administration on the ventral prostate lobe of adult rat. Twenty adult male rats were divided into 2 groups: L-animals were daily injected with 50 µL of leptin (8 µg/100 g BW, subcutaneous) for four days and C-animals received the same volume of saline solution. Lipid profile and testosterone serum levels were evaluated. The prostate ventral lobe was processed for histomorphometric analysis. Gene expression of aromatase, androgen, leptin and estrogen receptors isoforms was evaluated by real-time PCR. Cell proliferation was evaluated by PCNA immunohistochemistry. Data were expressed as mean±standard error and analyzed by student's t-test. Serum levels of cholesterol (C=39.7±4.2;L=55.2±4.2, mg/dL; P<0.02) increased and testosterone (C=1.6±0.43;L=0.6±0.15, ng/dL; P<0.03) decreased in L group. The histomorphometric analysis showed a reduction in cell density (C=8868±242; L=8211±210, mm(2); P<0.04), in total (C=0.24±0.026; L=0.10±0.009, mm(2); P<0.001) and in the internal acini areas (C=0.16±0.009; L=0.08±0.006, mm(2); P<0.0002). On the other hand, there was an increase in the epithelial height (C=17.3±0.3; L=22.8±0.2, µm; P<0.0001) and in the number of acini (C=7.0±0.2; L=8.7±0.1, mm(2); P<0.0002). The histomorphometric analyses together with PCNA immunohistochemistry results suggest that leptin increases cell proliferation. In relation to the gene expression, leptin treatment increased the expression of all genes, but ER-α, in more than 200 times compared to the expression in C group. In conclusion, in this paper we showed that leptin has a direct effect on the prostate gland of adult rats leading to an increase in proliferation and in the gene expression of aromatase, androgen, leptin and estrogen receptors isoforms that are important for the physiology of the prostate gland.

Glutamine supplementation prevents collagen expression damage in healthy urinary bladder caused by radiotherapy.

OBJECTIVE: Patients who have had pelvic radiotherapy as part of their cancer therapy may develop subsequent urinary bladder effects such as hyperactive bladder, incontinence, and dysuria. Therefore, the goal of this study was to evaluate whether glutamine supplementation could prevent collagen expression damage in healthy urinary bladder caused by radiotherapy. METHODS: Fifteen adult Wistar rats were separated into a control group that received food and water ad libitum (C group), an irradiated group that received a single pelvic radiation dose of 1164 cGy (I group), and an irradiated group supplemented with l-glutamine every day during the entire experimental period (0.65 g/kg of body weight; I+G group). All animals were sacrificed 15 d after irradiation. The extracellular matrix and muscle were quantified by a morphometric method. Picro Sirius Red was used to visualize the different collagen types. Reverse transcription-polymerase chain reaction and immunohistochemistry were used to determine collagen type I and III expressions. RESULTS: The extracellular matrix (C group 36.84±4.37, I group 31.64±5.00, I+G group 35.53±2.60, P=0.0001), muscle (C group 36.43±6.15, I group 29.39±7.08, I+G group 31.38±3.14, P=0.0001), and gene expressions of collagen type I (C group 1.067±0.31, I group 0.579±0.17, I+G group 1.816±0.66, P=0.0009) and type III (C group 0.99±0.28, I group 0.54±0.13, I+G group 1.07±0.28, P=0.0080) were decreased in the I group. Apart from muscle, glutamine supplementation prevented these alterations. Immunohistochemistry and Picro Sirius Red showed similar results. CONCLUSION: Supplementation with l-glutamine seems to prevent bladder wall damage in relation to extracellular matrix volumetric density and collagen expression. These results suggest that glutamine supplementation could be efficient in protecting healthy tissues from the adverse effects of radiotherapy.

The impact of dietary organic and transgenic soy on the reproductive system of female adult rat.

The goal of this article was to compare the effects of a prolonged use of organic and transgenic soy on the lipid profile and ovary and uterus morphology. Wistar rats were fed three different diets from weaning until sacrifice at 15 months of age. The three diets were: casein-based diet control group (CG), organic soy-based diet group (OSG), or transgenic soy-based diet group (GMSG). There were no differences in food consumption or in the diet isoflavone components among the groups. Compared with the CG diet, both the OSG and GMSG diets were associated with significant reductions in body weight, serum triglycerides, and cholesterol (P < 0.05) (CG = 406 +/- 23.1; 104.3 +/- 13.2; 119.9 +/- 7.3 GMSG = 368 +/- 17.6; 60.3 +/- 4.6; 83.3 +/- 5.7 OSG = 389 +/- 23.5; 72.3 +/- 12.5; 95.5 +/- 8.0, respectively). The volume density of endometrial glandular epithelium was greater in the GMSG group (29.5 +/- 7.17, P < 0.001) when compared with the CG (18.5 +/- 7.4) and OSG (20.3 +/- 10.6) groups. The length density of endometrial glandular epithelium was shorter in both GMSG (567.6 +/- 41.1) and OSG (514.8 +/- 144.5) diets compared with the CG (P < 0.05) diet. GMSG also resulted in reduced follicle number and increased corpus luteum number compared to the OSG or CG diets (P < 0.05). In summary, both GMSG and OSG diets resulted in decreased body weight and lower serum triglyceride and cholesterol levels, and alterations in uterine and ovarian morphology were also observed. The prolonged use of soy-based diets and their relation to reproductive health warrants further investigation.