Limitations Imposed by Testicular Blood Flow on the Function of Leydig Cells in Rats in vivo

Bp, Setchell; Ka, Galil

doi:10.1071/bi9830285

Cited by 34 publications

(21 citation statements)

References 17 publications

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“…There is already other evidence to this effect as testicular blood flow appears to be correlated with the mass of seminiferous tubules (Setchell & Galil, 1983), although no physiological basis for this observation has been reported. Exactly how the seminiferous tubules control the vasculature, what paracrine factors mediate this control, and what aspects of vascular function are involved, remain to be determined.…”

Section: Discussionmentioning

confidence: 90%

“…There is already some evidence to this effect, as testicular blood flow appears to be correlated with the overall mass of seminiferous tubules (Setchell & Galil, 1983). In the present study we have assessed the role of the seminiferous tubules in regulating IF volume using a model system in which the Leydig cells of adult rats were destroyed with EDS (Jackson & Morris, 1977;Morris, Phillips & Bardin, 1986), thus removing their possible influence on the vasculature.…”

Section: Introductionmentioning

confidence: 91%

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Interstitial fluid volume in the rat testis: androgen-dependent regulation by the seminiferous tubules?

Maddocks

Sharpe²

1989

Journal of Endocrinology

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Regulation of testicular interstitial fluid (IF) volume has been investigated in adult male rats in which the Leydig cells were selectively destroyed with a single i.p. injection of ethane dimethane sulphonate (EDS). Following this treatment, some animals also received testosterone supplementation by s.c. injection every 3 days, beginning either from the time of EDS injection, or 3-12 days afterwards. The volume of IF obtained by drip collection was determined, and testosterone and gonadotrophin concentrations measured in blood and in IF. Testosterone levels in IF and serum became undetectable by 3 days after EDS treatment. IF volume was reduced by 50% (P less than 0.01) to reach a minimum level between 6 and 9 days after treatment. However, this decline was prevented in the absence of Leydig cells by supplementation with testosterone from the time of EDS injection, a treatment which also kept gonadotrophins at minimum or undetectable levels. Furthermore, the reduced IF volume seen up to 9 days after treatment with EDS alone could be restored to control levels within 3 days by a single injection of testosterone. The results obtained demonstrate that androgens, but not Leydig cells or gonadotrophins, are required for the maintenance of interstitial fluid volume in the adult rat testis. It is suggested that the seminiferous tubules may mediate this response, through an androgen-dependent mechanism.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 91%

Interstitial fluid volume in the rat testis: androgen-dependent regulation by the seminiferous tubules?

Maddocks

Sharpe²

1989

Journal of Endocrinology

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“…Testi¬ cular blood flow is correlated with testis weight (Setchell & Galil, 1983) and, during sexual maturation, blood flow will presumably increase in parallel with testis weight. This may affect arterio-venous transfer of blood in the spermatic cord, and the results of the present study do indicate that testosterone levels are diluted more in older animals (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Despite these advances and the realization that testosterone is essential for the maintenance of spermatogenesis (see Sharpe, 1987), the question as to the level of testicular testosterone that is necessary to maintain spermatogenesis and how to measure intratesticular testosterone levels is still controversial and much debated (Sharpe, 1987;Maddocks & Setchell, 1988aA 1989Rommerts, 1988;Sharpe, Donachie & Cooper, 1988). There has also been an increasing awareness of the importance of the testicular vasculature for normal testicular function (see Bergh, Damber & Widmark, 1988;Maddocks & Setchell, 1988a;Maddocks & Sharpe, 1989), and Leydig cell function (and testosterone production/secretion) is known to be affected by changes in testicular blood flow (Setchell & Galil, 1983); indeed, certain aspects of the microcirculation of the testis may be under androgen-dependent paracrine control (Maddocks & Sharpe, 1989). We have therefore readdressed the question of how to measure androgen levels accurately within the testis, and how this androgen reaches the peripheral circulation, by comparing the concentrations of testosterone in vari¬ ous vascular and extracellular compartments in a variety of situations in rats.…”

Section: Introductionmentioning

confidence: 98%

Dynamics of testosterone secretion by the rat testis: implications for measurement of the intratesticular levels of testosterone

Maddocks

Sharpe²

1989

Journal of Endocrinology

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Testosterone concentrations have been measured in testicular interstitial fluid (IF), and in blood plasma sampled from various parts of the rat testis and spermatic cord, to assess (1) the most accurate method for determination of the intratesticular levels of testosterone, and (2) the route of secretion of testosterone from the testis. In untreated adult rats, testosterone concentrations were highest in blood collected from veins on the surface of the testis (269.50 +/- 30.63 (S.E.M.) nmol/l), but were reduced by 56% on average in blood collected from veins at the proximal end of the spermatic cord (123.06 +/- 24.75 nmol/l), and were reduced considerably in peripheral venous blood (4.55 +/- 0.55 nmol/l). Similar changes occurred in adult rats in which steroidogenesis was either stimulated (by treatment with human chorionic gonadotrophin; hCG) or inhibited (by treatment with aminoglutethimide; AMG), and in rats of various ages during sexual maturation. The reduction in testosterone levels during passage of blood from the testis up the spermatic cord is probably due mainly to dilution by incoming arterial blood which transfers to venous blood via anastomoses in the spermatic cord. Venous-arterial transfer of testosterone in the cord contributed to this in only a minor way. Concentrations of testosterone in testicular IF were always greater than testicular venous concentrations in control, developing and hCG-stimulated rats, but were comparable in rats treated with AMG to suppress Leydig cell steroidogenesis. These and other results demonstrate that the method of drip-collection of IF results in over-estimation of the actual intratesticular levels of testosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…After disruption of the testis, and thus the paracrine environment, specific alterations in LC number, morphology, or testosterone production must occur to maintain intratesticular and circulating testosterone levels. For example, if the seminiferous tubules shrink in size due to experimentally induced loss of germ cells (Setchell and Galil, 1983), and there is a concomitant reduction in the transport of LH into the testis, testosterone production by the LCs decreases. These changes trigger either compensatory changes in LH levels and/or changes in LC number or size in order to restore steady-state testosterone levels.…”

Section: B Paracrine Regulation Of Lc Functionmentioning

confidence: 98%

Rodent Leydig Cell Tumorigenesis: A Review of the Physiology, Pathology, Mechanisms, and Relevance to Humans

Cook

Klinefelter

Hardisty

et al. 1999

Critical Reviews in Toxicology

175

122

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Leydig cells (LCs) are the cells of the testis that have as their primary function the production of testosterone. LCs are a common target of compounds tested in rodent carcinogenicity bioassays. The number of reviews on Leydig cell tumors (LCTs) has increased in recent years because of its common occurrence in rodent bioassays and the importance in assessing the relevance of this tumor type to humans. To date, there have been no comprehensive reviews to identify all the compounds that have been shown to induce LCTs in rodents or has any review systematically evaluated the epidemiology data to determine whether humans were at increased risk for developing LCTs from exposure to these agents. This review attempts to fill these deficiencies in the literature by comparing the cytology and ontogeny of the LC, as well as the endocrine and paracrine regulation of both normal and tumorigenic LCs. In addition, the pathology of LCTs in rodents and humans is compared, compounds that induce LC hyperplasia or tumors are enumerated, and the human relevance of chemical-induced LCTs is discussed. There are plausible mechanisms for the chemical induction of LCTs, as typified by agonists of estrogen, gonadotropin releasing hormone (GnRH), and dopamine receptors, androgen receptor antagonists, and inhibitors of 5alpha-reductase, testosterone biosynthesis, and aromatase. Most of these ultimately involve elevation in serum luteinizing hormone (LH) and/or LC responsiveness to LH as proximate mediators. It is expected that further work will uncover additional mechanisms by which LCTs may arise, especially the role of growth factors in modulating LC tumorigenesis. Regarding human relevance, the pathways for regulation of the hypothalamo-pituitary-testis (HPT) axis of rats and humans are similar, such that compounds that either decrease testosterone or estradiol levels or their recognition will increase LH levels. Hence, compounds that induce LCTs in rats by disruption of the HPT axis pose a risk to human health, except for possibly two classes of compounds (GnRH and dopamine agonists). Because GnRH and prolactin receptors are either not expressed or are expressed at very low levels in the testes in humans, the induction of LCTs in rats by GnRH and dopamine agonists would appear not to be relevant to humans; however, the potential relevance to humans of the remaining five pathways of LCT induction cannot be ruled out. Therefore, the central issue becomes what is the relative sensitivity between rat and human LCs in their response to increased LH levels; specifically, is the proliferative stimulus initiated by increased levels of LH attenuated, similar, or enhanced in human vs. rat LCs? There are several lines of evidence that suggest that human LCs are quantitatively less sensitive than rats in their proliferative response to LH, and hence in their sensitivity to chemically induced LCTs. This evidence includes the following: (1) the human incidence of LCTs is much lower than in rodents even when corrected for detection bias; (2) several ...

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Limitations Imposed by Testicular Blood Flow on the Function of Leydig Cells in Rats in vivo

Cited by 34 publications

References 17 publications

Interstitial fluid volume in the rat testis: androgen-dependent regulation by the seminiferous tubules?

Interstitial fluid volume in the rat testis: androgen-dependent regulation by the seminiferous tubules?

Dynamics of testosterone secretion by the rat testis: implications for measurement of the intratesticular levels of testosterone

Rodent Leydig Cell Tumorigenesis: A Review of the Physiology, Pathology, Mechanisms, and Relevance to Humans

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