Altered bioavailability of testosterone in androgen-binding protein-transgenic mice

Jeyaraj, D. A.; Grossman, Gail; Petrusz, Peter

doi:10.1016/j.steroids.2005.03.015

Cited by 37 publications

(28 citation statements)

References 43 publications

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“…In the DES 1.5 group at 6 weeks of age, the total plasma testosterone level decreased, but the total intratesticular testosterone level did not. These results are in agreement with those of Jeyaraj et al (2005). Therefore, we speculate that the level of intratesticular free testosterone, which was not measured in this experiment, was decreased, but not to a level that would disrupt spermatogenesis.…”

Section: Discussionsupporting

confidence: 92%

“…ABP-transgenic mice have increased total intratesticular testosterone concentrations but decreased free testosterone levels, suggesting that the decrease in the availability of free testosterone lowers germ cell numbers and reduces fertility [53]. Furthermore, in the present experiment, the ABP mRNA expression level was significantly higher in the DES 1.5 group at 6 weeks of age compared with the other groups and in the DES 0.5 and 1.5 groups at 15 weeks of age compared with the control group.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Maternal Exposure to Low Doses of DES on Testicular Steroidogenesis and Spermatogenesis in Male Rat Offspring

Kobayashi

Shirai

Sakaue

et al. 2009

Journal of Reproduction and Development

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Abstract.Our previous studies have demonstrated that prenatally administered diethylstilbestrol (DES) impairs testicular endocrine function in male offspring. The present study examined whether maternal DES treatment influences testicular steroidogenesis and spermatogenesis. DES was injected subcutaneously at 0.5 or 1.5 μg/kg/day (DES 0.5 and 1.5 groups, respectively) into pregnant SD rats on days 7-21 of gestation. Male offspring in the DES 0.5 and 1.5 groups were autopsied at 1, 3, 6 and 15 weeks after birth. At 1 week, DES treatment did not lead to a change in the volume of P450scc-positive cells (Leydig cells), suggesting that DES has no inhibitory effect on the development of Leydig cells. DES administration disrupted luteinizing hormone receptor (LHr) expression and exerted inhibitory effects on signal transduction from LHr to steroidogenic acute regulatory protein (StAR) in testicular steroidogenesis (P<0.05), although there were no changes in the mRNA expression levels of steroidogenic enzymes, such as P450scc, 3β-hydroxysteroid dehydrogenase (3β-HSD) and P45017α, which may have caused a decrease in the plasma testosterone level. DES treatment did not disrupt the cycle of spermatogenesis but did upregulate the expression levels of androgen receptor (AR) mRNA in both DES groups at 15 weeks (P<0.05). These results indicate that maternal DES treatment disrupts steroidogenesis but induces a high level of AR mRNA expression to counteract the low levels of testosterone during spermatogenesis. uring embryonic development, rat primordial germ cells appear in the yolk sac on embryonic day 10, and the gonadal primordium begins to develop as the genital ridge around embryonic day 11. Primordial germ cells begin to reach the genital ridge on embryonic day 12 [1]; thereafter, Sertoli and Leydig cells in the male differentiate from genital ridge cells, leading to a series of differentiation events. The duration of pregnancy is generally divided into periods of embryonic development (first trimester), organogenesis (second trimester) and organ maturation (third trimester).Diethylstilbestrol (DES), a synthetic non-steroidal estrogen, exhibits strong estrogenic activity by binding to estrogen receptors (ERs). It has been shown that the treatment of pregnant rats with DES dose-dependently (range: 10 to 300 μg/kg) suppresses testosterone levels in the blood and testes of male fetuses [2-4]. We administered doses of DES much lower (1.5 μg/kg) than those previously applied to pregnant rats at 7-21 days of gestation (in the second and third trimesters) and demonstrated that DES suppresses plasma testosterone levels in adolescent male offspring (6 weeks after birth) [5].Androgen plays an important role in the development and function of the testis and male reproductive tract via the androgen receptor (AR). Similarly, since ERs have been found in these tissues [6][7][8][9][10], estrogen may be involved in development of the male reproductive system. Nevertheless, it is apparent that male ER-or aromatase-knockout mice initially ...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Effects of Maternal Exposure to Low Doses of DES on Testicular Steroidogenesis and Spermatogenesis in Male Rat Offspring

Kobayashi

Shirai

Sakaue

et al. 2009

Journal of Reproduction and Development

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“…Androgen binding proteins are required for the maintenance of high concentrations of testosterone in the testis, a requirement for the maintenance of optimal spermatogenesis after its initiation by FSH (Plant and Marshall, 2001). A reduction in intra-testicular testosterone normally results in reduced spermatogenesis (Jeyaraj, 2005) and could explain the reduced density of stored spermatozoa among BaP-exposed rats in this study compared with controls. Furthermore, decreased testosterone levels similar to that observed in the present study upon prolonged exposure to BaP may have implications on successful mating of females by BaP-exposed males (Karabelyos and Csaba, 1996).…”

Section: Discussionmentioning

confidence: 67%

Alteration of fertility endpoints in adult male F-344 rats by subchronic exposure to inhaled benzo(a)pyrene

Ramesh

Inyang

Lunstra

et al. 2008

Experimental and Toxicologic Pathology

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The objective of this study was to evaluate the reproductive risk associated with exposure of adult male Fisher-344 rats to inhaled benzo(a)pyrene (BaP). Rats were assigned randomly to a treatment or control group. Treatment consisted of sub-chronic exposure of rats via inhalation to 75μg BaP/ m 3 , 4 hours daily for 60 days, while control animals were unexposed (UNC). Blood samples were collected immediately after the cessation of exposures (time 0) and subsequently at 24, 48, and 72 hrs, to assess the effect of bioavailable BaP on plasma testosterone and luteinizing hormone (LH) concentrations. Rats were sacrificed after the last blood collection. Testes were harvested, weighed and prepared for histology and morphometric analysis, and cauda epididymides were isolated for the determination of progressive motility and density of stored spermatozoa. BaP exposure reduced testis weight compared with UNC (Mean ± SE; 2.01 ± 0.11 vs. 3.04 ± 0.16 g; P< 0.025), and caused significant reductions in the components of the steroidogenic and spermatogenic compartments of the testis. Progressive motility and mean density of stored spermatozoa were reduced (P< 0.05). Plasma testosterone concentrations were decreased by two-thirds in BaPexposed rats throughout the time periods studied compared with those of their UNC counterparts (P< 0.05), concomitant with increased concentrations of LH in BaP-exposed rats (P< 0.05). These data suggest that sub-chronic exposure to inhaled BaP contribute to reduced testicular and epididymal function in exposed rats.

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“…Expression of the Aoh3 gene is restricted to the Bowman's gland, the main secretory organ of the nasal mucosa. The protein has been purified to homogeneity from this source and shown to have an overlapping set of substrates with AOX1 and AOH1 (31). No information is available on the product of the mouse Aoh2 gene, whose protein has never been isolated.…”

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confidence: 99%

Role of the Molybdoflavoenzyme Aldehyde Oxidase Homolog 2 in the Biosynthesis of Retinoic Acid: Generation and Characterization of a Knockout Mouse

Terao

Kurosaki

Barzago

et al. 2009

Molecular and Cellular Biology

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The mouse aldehyde oxidase AOH2 (aldehyde oxidase homolog 2) is a molybdoflavoenzyme. Harderian glands are the richest source of AOH2, although the protein is detectable also in sebaceous glands, epidermis, and other keratinized epithelia. The levels of AOH2 in the Harderian gland and skin are controlled by genetic background, being maximal in CD1 and C57BL/6 and minimal in DBA/2, CBA, and 129/Sv strains. Testosterone is a negative regulator of AOH2 in Harderian glands. Purified AOH2 oxidizes retinaldehyde into retinoic acid, while it is devoid of pyridoxal-oxidizing activity. Aoh2 ؊/؊ mice, the first aldehyde oxidase knockout animals ever generated, are viable and fertile. The data obtained for this knockout model indicate a significant role of AOH2 in the local synthesis and biodisposition of endogenous retinoids in the Harderian gland and skin. The Harderian gland's transcriptome of knockout mice demonstrates overall downregulation of direct retinoid-dependent genes as well as perturbations in pathways controlling lipid homeostasis and cellular secretion, particularly in sexually immature animals. The skin of knockout mice is characterized by thickening of the epidermis in basal conditions and after UV light exposure. This has correlates in the corresponding transcriptome, which shows enrichment and overall upregulation of genes involved in hypertrophic responses.Aldehyde oxidases (AOXs) (EC 1.2.3.1) are structurally conserved proteins belonging to the family of molybdoflavoenzymes along with xanthine oxidoreductase (XOR), the key enzyme in the catabolism of purines (25,28). In their catalytically active form, both AOXs and XORs are dimers of identical subunits characterized by three conserved domains separated by nonconserved hinge regions (28). The amino-terminal 25-kDa domain contains two nonidentical 2Fe-2S redox centers. The flavin adenine dinucleotide binding region is located in the intermediate 45-kDa domain, while the substrate and the molybdopterin cofactor binding pocket reside in the carboxy-terminal 85-kDa domain (28). AOXs have broad substrate specificity, hydroxylating N-heterocycles or oxidizing aliphatic as well as aromatic aldehydes into the corresponding acids (35,41,42).The primary structures of mammalian AOXs and XORs are more than 40% identical, and the two types of enzymes are evolutionary related. Most of the available data indicate that AOXs evolved from a primordial form of XOR through a series of gene duplication events (28). In mammals, the number of AOX genes is variable and species specific (25,28,37,65). Rodents have four AOX genes (Aox1, Aoh1, Aoh2, and Aoh3) which are the products of asynchronous duplication events and cluster at a short distance from one another on the same chromosome (chromosome 1c1 in mice and chromosome 9 in rats) (Fig. 1). The Aoh1, Aoh2, and Aoh3 genes are also known as Aox3, Aox4, and Aox3l, respectively, and are currently designated with the latter names in the NCBI database.(The designation of the four mouse AOX genes as Aox1, Aox3, Aox4, and Aox3l in...

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Altered bioavailability of testosterone in androgen-binding protein-transgenic mice

Cited by 37 publications

References 43 publications

Effects of Maternal Exposure to Low Doses of DES on Testicular Steroidogenesis and Spermatogenesis in Male Rat Offspring

Effects of Maternal Exposure to Low Doses of DES on Testicular Steroidogenesis and Spermatogenesis in Male Rat Offspring

Alteration of fertility endpoints in adult male F-344 rats by subchronic exposure to inhaled benzo(a)pyrene

Role of the Molybdoflavoenzyme Aldehyde Oxidase Homolog 2 in the Biosynthesis of Retinoic Acid: Generation and Characterization of a Knockout Mouse

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