Age-related changes in conversion of 5 -androstan-17 -ol-3-one to 5 -androstane-3 ,17 -diol and 5 -androstane-3 ,17 -diol by rat testicular cells in vitro

Cochran, Roger C.; Schuetz, Allen W.; Ewing, Larry L.

doi:10.1530/jrf.0.0570143

Cited by 26 publications

(10 citation statements)

References 15 publications

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“…In addition, we attempted to describe the relationship between Leydig cell T production and peripheral androgen levels by measuring serum T concentrations in animals that were processed to obtain Leydig cells. In all cases, T concentrations were assayed in aliquots of spent media and serum samples by a previously described tritium-based RIA with an interassay variation of 7%-8% [48]. In order to localize BPA-induced lesions, we analyzed the levels of LHCGR, steroidogenic acute regulatory protein (STAR) and steroidogenic enzymes (CYP11A1, HSD3B, CYP17A1, and HSD17B3) in Western blots of ALCs isolated at 90 days of age from control and adult male rats exposed to BPA in the perinatal period (i.e., GD 12-PND 21).…”

Section: Measurement Of Steroidogenic Capacitymentioning

confidence: 99%

The Industrial Chemical Bisphenol A (BPA) Interferes with Proliferative Activity and Development of Steroidogenic Capacity in Rat Leydig Cells1

Nanjappa

Simon

Akingbemi

2012

Biology of Reproduction

118

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The presence of bisphenol A (BPA) in consumer products has raised concerns about potential adverse effects on reproductive health. Testicular Leydig cells are the predominant source of the male sex steroid hormone testosterone, which supports the male phenotype. The present report describes the effects of developmental exposure of male rats to BPA by gavage of pregnant and lactating Long-Evans dams at 2.5 and 25 μg/kg body weight from Gestational Day 12 to Day 21 postpartum. This exposure paradigm stimulated Leydig cell division in the prepubertal period and increased Leydig cell numbers in the testes of adult male rats at 90 days. Observations from in vitro experiments confirmed that BPA acts directly as a mitogen in Leydig cells. However, BPA-induced proliferative activity in vivo is possibly mediated by several factors, such as 1) protein kinases (e.g., mitogen-activated protein kinases or MAPK), 2) growth factor receptors (e.g., insulin-like growth factor 1 receptor-beta and epidermal growth factor receptors), and 3) the Sertoli cell-secreted anti-Mullerian hormone (also called Mullerian inhibiting substance). On the other hand, BPA suppressed protein expression of the luteinizing hormone receptor (LHCGR) and the 17beta-hydroxysteroid dehydrogenase enzyme (HSD17B3), thereby decreasing androgen secretion by Leydig cells. We interpret these findings to mean that the likely impact of deficits in androgen secretion on serum androgen levels following developmental exposure to BPA is alleviated by increased Leydig cell numbers. Nevertheless, the present results reinforce the view that BPA causes biological effects at environmentally relevant exposure levels and its presence in consumer products potentially has implication for public health.

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Section: Measurement Of Steroidogenic Capacitymentioning

confidence: 99%

The Industrial Chemical Bisphenol A (BPA) Interferes with Proliferative Activity and Development of Steroidogenic Capacity in Rat Leydig Cells1

Nanjappa

Simon

Akingbemi

2012

Biology of Reproduction

118

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“…Testosterone, androstenedione, and androstanediol were measured by RIA in plasma, in conditioned medium from in vitro LC cultures, and in supernatants of total testicular homogenates (Coffey et al 1971, Cochran et al 1979, 1981. All samples were assayed in duplicate, and each experimental data point consisted of 3-6 samples.…”

Section: Hormone Assaysmentioning

confidence: 99%

Androgen profiles during pubertal Leydig cell development in mice

Arumugam²,

Zhang³

et al. 2010

Reproduction

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Postnatal Leydig cell (LC) development in mice has been assumed empirically to resemble that of rats, which have characteristic hormonal profiles at well-defined maturational stages. To characterize the changes in LC function and gene expression in mice, we examined reproductive hormone expression from birth to 180 days, and quantified in vivo and in vitro production of androgens during sexual maturation. Although the overall plasma androgen and LH profiles from birth through puberty were comparable to that of rats, the timing of developmental changes in androgen production and steroidogenic capacity of isolated LCs differed. In mice, onset of androgen biosynthetic capacity, distinguished by an acute rise in androstenedione and testosterone production and an increased expression of the steroidogenic enzymes, cytochrome P450 cholesterol side-chain cleavage enzyme and 17a-hydroxylase, occurred at day 24 (d24) rather than at d21 as reported in rats. Moreover, in contrast to persistently high testosterone production by pubertal and adult rat LCs, testosterone production was maximal at d45 in mice, and then declined in mature LCs. The murine LCs also respond more robustly to LH stimulation, with a greater increment in LH-stimulated testosterone production. Collectively, these data suggest that the mouse LC lineage has a delayed onset, and that it has an accelerated pace of maturation compared with the rat LC lineage. Across comparable maturational stages, LCs exhibit species-specific developmental changes in enzyme expression and capacity for androgen production. Our results demonstrate distinct differences in LC differentiation between mice and rats, and provide informative data for assessing reproductive phenotypes of recombinant mouse models.

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“…Testosterone, androstenedione, and 5␣-androstane-3␣-17␤-diol (androstanediol) rather than 5␣-androstane-3␤-17␤-diol were measured in conditioned media from in vitro cultures and supernatant of total testicular homogenates (22)(23)(24). All samples were assayed in duplicate.…”

Section: Hormonal Determinationmentioning

confidence: 99%

Pubertal and Adult Leydig Cell Function in Mullerian Inhibiting Substance-Deficient Mice

Arumugam

Baker

et al. 2005

Endocrinology

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Mullerian inhibiting substance (MIS) causes Mullerian duct regression during sexual differentiation and regulates postnatal Leydig cell development. MIS knockout (MIS-KO) mice with targeted deletions of MIS developLeydig cell hyperplasia, but their circulating androgen concentrations are reportedly unaltered. We compared reproductive hormone profiles, androgen biosynthesis, and the expression of key steroidogenic and metabolic enzymes in MIS-KO and wild-type (WT) mice at puberty (36 d) and sexual maturity (60 d). In pubertal animals, basal testosterone and LH concentrations in plasma were lower in MIS-KO than WT mice, whereas human chorionic gonadotropin-stimulated testosterone concentrations were similar. In adults, basal LH, and both basal and human chorionic gonadotropin (hCG)-stimulated testosterone concentrations were similar. Purified Leydig cells from pubertal MIS-KO mice had lower testosterone but higher androstanediol and androstenedione production rates. In contrast, testosterone, androstanediol, and androstenedione production rates were all lower in adult MIS-KO Leydig cells. Steroidogenic acute regulatory protein expression was lower in pubertal MIS-KO mice compared with WT, whereas 17␤-hydroxysteroid dehydrogenase and 5␣-reductase were greater, and P450c17 and P450scc were similar. The expression of steroidogenic acute regulatory protein and 17␤-hydroxysteroid dehydrogenase was lower in adult MIS-KO mice, whereas that of 5␣-reductase, P450c17, and P450scc was similar. MIS not only induces regression of the Mullerian ducts during male sexual differentiation (3-5) but also plays a critical paracrine role in the regulation of Leydig cell development and testosterone biosynthesis (6 -10). MIS has also been shown to inhibit proliferation of prepubertal progenitor Leydig cells and prevent regeneration of Leydig cells after chemical ablation (11,12). These actions of MIS in the testis are mediated directly through the MIS type II receptor, which is abundantly expressed in Leydig cells (7). Male transgenic mice overexpressing MIS have feminized genitalia secondary to fewer Leydig cell numbers and decreased serum testosterone concentrations (4, 13). Conversely, mice with targeted deletions of MIS [MIS knockout (MIS-KO)] and/or its receptor develop Mullerian structures but also manifest Leydig cell hyperplasia, focal Leydig cell tumors, and infertility (14,15). Recently, MIS has been shown to induce FSH mRNA expression and enhance LH␤ promoter activity in a pituitary cell line, indicating that changes in MIS action may also affect the hypothalamic-pituitary-gonadal axis (16).In adult MIS-KO mice, although Leydig cell numbers are increased and the mRNA expression of a key steroidogenic enzyme, P450c17, is more abundant, peripheral testosterone and LH concentrations are reportedly unaffected (8). These observations were surprising in light of the findings of decreased serum testosterone in MIS transgenic mice and the inhibitory actions of MIS on testosterone biosynthesis in both in vitro (6,8,10) and in vivo sy...

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Age-related changes in conversion of 5 -androstan-17 -ol-3-one to 5 -androstane-3 ,17 -diol and 5 -androstane-3 ,17 -diol by rat testicular cells in vitro

Cited by 26 publications

References 15 publications

The Industrial Chemical Bisphenol A (BPA) Interferes with Proliferative Activity and Development of Steroidogenic Capacity in Rat Leydig Cells1

The Industrial Chemical Bisphenol A (BPA) Interferes with Proliferative Activity and Development of Steroidogenic Capacity in Rat Leydig Cells1

Androgen profiles during pubertal Leydig cell development in mice

Pubertal and Adult Leydig Cell Function in Mullerian Inhibiting Substance-Deficient Mice

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