The Pituitary-Testicular Axis in the Streptozotocin Diabetic Male Rat: Evidence for Gonadotroph, Sertoli Cell and Leydig Cell Dysfunction

Murray, Frederick T.; Orth, Joanne M.; Gunsalus, Glen L.; Weisz, Judith; Li, J.B.; Jefferson, Leonard S.; Musto, Neal A.; Bardin, C. Wayne

doi:10.1016/s0022-5347(17)52979-1

Cited by 10 publications

(21 citation statements)

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“…Several studies have demonstrated a stepwise decrease in mean testosterone level per progressive increase in fasting plasma glucose throughout the whole range of plasma glucose [60,62,63]. In laboratory animals, diabetes has been associated with reductions in testicular Leydig cell number [66,67,68] and in testosterone secretion [68,69], possibly due to a direct adverse effect of glycaemia [68].…”

Section: Discussionmentioning

confidence: 99%

Diabetes mellitus and risk of prostate cancer: a meta-analysis

2004

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Aims/hypothesis. The association of diabetes mellitus with prostate cancer has been controversial. This study examines the strength of this association by conducting a detailed meta-analysis of the studies published in peer-reviewed literature on the subject. Methods. A comprehensive search for articles published up to 2003 was performed, reviews of each study were conducted and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) was calculated using the random-and the fixedeffects models. Subgroup and sensitivity analyses were also performed. Results. We included 14 studies, published between 1971 and 2002, in the meta-analysis (five case-control studies, nine cohort studies). We found no evidence of publication bias (p=0.89) or heterogeneity among the studies (p=0.38). The association of diabetes with prostate cancer was statistically significant, both on the basis of a random-effects model (RR=0.91, 95% CI: 0.86 to 0.96), and on the basis of a fixed-effects model (RR=0.91, 95% CI: 0.88 to 0.94). When the analysis was stratified into subgroups according to study design, the association was inverse in both cohort and case-control studies, but only in the former was it statistically significant. The sensitivity analysis strengthened our confidence in the validity of this association. Conclusions/interpretation. Our meta-analysis findings provide strong evidence that people with diabetes have a significant decrease in risk of developing prostate cancer. There is biological evidence to support this association.

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Section: Discussionmentioning

confidence: 99%

Diabetes mellitus and risk of prostate cancer: a meta-analysis

2004

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“…The failure of the hypothalamic pituitary gonadal axis maintaining proportionate levels of these endogenous hormones may result in disruption of spermatogenic and sexual function; and ultimately leads to infertility [18]. Systemic metabolic imbalance in long-standing severe hyperglycaemia affects the hypothalamic pituitary testis axis function, disturbs the jurisdiction function of the endocrine system, and influences steroidogenic capacity of Leydig cells [19][20][21]. Studies have suggested that STZ induced diabetes caused 2 major changes in Leydig cells: 1) a decrease in total Leydig cells number, and 2) an impairment in cells function [21].…”

Section: Animal Treatmentmentioning

confidence: 99%

“…FSH secreted by sertoli cells is a major role player in the development of testes, which promotes the combination of androgen binding protein (ABP) with testosterone and maintains the level of testosterone in spermatogenic cells. Both clinical and basic studies have demonstrated that diabetes induces a decrease in the serum LH and FSH levels with raised FSH/LH ratio, and this alteration is responsible for the diabetes-related effects on libido and spermatogenesis [21][22][23][24]. A better understanding of the hormonal requirements of spermatogenesis and libido is desirable for the improvement of treatment for male infertility [25,26].…”

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confidence: 99%

Protective effects of <i>Lycium barbarum</i> polysaccharide on male sexual dysfunction and fertility impairments by activating hypothalamic pituitary gonadal axis in streptozotocin-induced type-1 diabetic male mice

Shi

Zheng

et al. 2017

Endocr J

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“…16 These effects have not hindered the usefulness of using this animal model in many studies. With our modi®cation of injecting 25 mgakg streptozotocin twice at a two week interval, the rats used in our study were not as sick as those described in previous reports.…”

Section: Diabetes-induced Impotence: Molecular Mechanisms Ai El-sakkamentioning

confidence: 99%

Effects of diabetes on nitric oxide synthase and growth factor genes and protein expression in an animal model

et al. 1999

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Erectile dysfunction occurs frequently in humans with diabetes mellitus; the molecular basis of this phenomenon is not known. We investigated the effects of diabetes on penile erection, nitric oxide synthase and growth factors expression in an animal model. Forty male rats were divided into two groups: the experimental group (n 30) received intraperitoneal injection of Streptozotocin (STZ) dissolved in citrate buffer to induce diabetes; ten age-matched control rats received injection of citrate buffer vehicle only. Before euthanization at eight weeks, erectile function was assessed by electrostimulation of the cavernous nerves. NADPH diaphorase staining was used to identify NOS and immunostaining technique was used to identify nNOS in the penile nerve ®bers. RT-PCR was used to identify mRNA expression of nNOS, eNOS, iNOS, ER-b b, ER-a, NGF, IGF-I, TGF-b1, and AR. Western blot was used to identify nNOS, IGF-I, NGF, and TFG-b protein expressions. In the diabetic group, there was: (1) a signi®cant decrease in NOS containing nerve ®bers in the dorsal and intracavernosal nerves; (2) a signi®cant lower maximal intracavernosal pressure. RT-PCR showed down-regulation of nNOS (large form), iNOS and ER-b mRNA expression, Immunoblot showed down-regulation of nNOS protein expression and nNOS immunostaining showed less positive staining in the dorsal and intracavernous nerves in the diabetic group. These molecular changes may provide the basis for further studies to explore the association between diabetes and impotence.

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The Pituitary-Testicular Axis in the Streptozotocin Diabetic Male Rat: Evidence for Gonadotroph, Sertoli Cell and Leydig Cell Dysfunction

Cited by 10 publications

References 0 publications

Diabetes mellitus and risk of prostate cancer: a meta-analysis

Diabetes mellitus and risk of prostate cancer: a meta-analysis

Protective effects of <i>Lycium barbarum</i> polysaccharide on male sexual dysfunction and fertility impairments by activating hypothalamic pituitary gonadal axis in streptozotocin-induced type-1 diabetic male mice

Effects of diabetes on nitric oxide synthase and growth factor genes and protein expression in an animal model

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