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

Maddocks, S.; Sharpe, R. M.

doi:10.1677/joe.0.1220323

Cited by 27 publications

(12 citation statements)

References 23 publications

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“…However, it is the intratesticular level of testosterone which is important for fertility and this cannot be deduced in any precise way from the levels in peripheral blood. This has been demonstrated clearly from our recent studies in the rat (Maddocks & Sharpe, 1989) (see Fig. 1) and has been confirmed in normal men, from whom testicular, spermatic and peripheral venous blood were collected at the time of vasectomy reversal .…”

Section: E F I C I E N C I E S I N I N T R a T E S T I C U L A R C supporting

confidence: 77%

“…required for spermatogenesis is controlled by the vasculature, as all such compounds must first pass across the vascular endothelium into testicular interstitial fluid (IF) before gaining access to the seminiferous tubules. It has now been shown that IF formation is androgen-regulated, presumably via effects of testosterone on the Sertoli or peritubular cells which then modulate the vasculature by secreting one or more vasoactive factors (Maddocks & Sharpe, 1989). More recently it has been shown that this effect of testosterone involves modulation of testicular blood flow (J. E. Damber, A. Widmark and S. Maddocks, unpublished data).…”

Section: T H E I N T R a T E S T I C U L A R Role(s) O F T E S T O S mentioning

confidence: 98%

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Intratesticular Control Of Steroidogenesis

Sharpe

1990

Clinical Endocrinology

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Men are men because of testosterone, and the effects of this hormone are evident in virtually every organ or tissue in a normal adult man. Because testosterone is a classical endocrine hormone with effects throughout the body, many endocrinologists will have failed to realize that, in terms of its effects on fertility, the primary role of testosterone is not endocrine but paracrine, as it is the local action of testosterone on spermatogenesis which determines fertility. When looked at from this perspective it is logical to question the traditional endocrine teaching which states that testosterone secretion is controlled solely by pituitary luteinizing hormone (LH). Certainly, the levels of testosterone and LH in peripheral blood show a close relationship, but it is not the level of testosterone in peripheral blood which determines fertility. If the primary role of testosterone is within the testis, then it is not unreasonable to expect that local mechanisms may exist to regulate the intratesticular levels of this steroid. The object of this review is to examinecritically the evidence for such mechanisms, their possible nature and their physiological and clinical significance (if any).Before reviewing the data on intratesticular control of steroidogenesis it is essential to place it in perspective. To do this, three principal questions need to be answered: ( I ) Why might intratesticular mechanisms for local control of testosterone production be required? (2) What is the role (or roles) of testosterone within the testis? A proper understanding of how testosterone controls spermatogenesis is essential if the local regulation of testosterone production is to be evaluated from a physiological perspective. ( 3 ) What are the constraints or problems relating to studies on the intratesticular control of steroidogenesis? It is essential to understand the potential limitations of studies on this subject so that a reasoned interpretation of the results can be made. Most relevant data is derived from studies in uitro, and the relationship of such data to the situation in uivo is often difficult to establish. W H Y M I G H T INTRATESTICULAR M E C H A N I S M S F O R T H E C O N T R O L OF TESTOSTERONE P R O D U C T I O N BE REQUIRED?It can be argued that paracrine control of testicular testosterone production is irrelevant, because (a) the serum levels of LH and testosterone clearly change together (i.e. they control each other) and (b) the removal of LH in animals by hypophysectomy or immunoneutralization lowers intratesticular testosterone levels so drastically that 787

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Section: E F I C I E N C I E S I N I N T R a T E S T I C U L A R C supporting

confidence: 77%

Section: T H E I N T R a T E S T I C U L A R Role(s) O F T E S T O S mentioning

confidence: 98%

Intratesticular Control Of Steroidogenesis

Sharpe

1990

Clinical Endocrinology

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“…Furthermore, this concentration of FSH is close to that used by Henriksen et al (1996) (2 ng/ml of FSH from another source), giving a near maximal effect in experiments of incubation of seminiferous tubular segments. As for testosterone, a 'physiologic' concentration (Maddocks & Sharpe 1989) was chosen.…”

Section: Discussionmentioning

confidence: 99%

The effects of FSH and of testosterone on the completion of meiosis and the very early steps of spermiogenesis of the rat: an in vitro study

Vigier¹,

Weiss²,

Perrard³

et al. 2004

Journal of Molecular Endocrinology

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The role of FSH and of testosterone in spermatogenesis has been a matter of controversy. In the present study, we addressed the involvement of these hormones in the regulation of the completion of meiosis of male rats under in vitro conditions. In the first series of experiments, middle/late pachytene spermatocytes were cocultured with Sertoli cells for 2 weeks in the absence or presence of FSH and/or testosterone. Treatment with both FSH and testosterone reduced slightly the percentage of apoptotic germinal cells in the cultures. Moreover, the number of round spermatids formed in vitro was enhanced by FSH or testosterone when compared with control cultures. Neither hormone influenced the half-life of round spermatids under the present culture conditions. The amounts of TP1 mRNAs in FSH-or FSH plus testosterone-treated cultures were higher than those of controls. In another series of experiments, round spermatids were incubated for 24 h in media conditioned by Sertoli cells cultured in the absence or presence of FSH and/or testosterone. TP1 mRNA contents of round spermatids incubated in media from Sertoli cells cultured in the presence of FSH and/or testosterone were two-to threefold higher than those of spermatids incubated in media from Sertoli cells cultured without hormones. These results indicate that FSH and testosterone have positive and somewhat overlapping effects on the meiotic divisions and the post-meiotic expression of a germ cell-specific gene, effects which cannot be related solely to their ability to reduce germinal cell apoptosis. Use of this culture system should help to test the effect of any hormone or factor on those steps in order to understand better their regulation.

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“…Testicular vein (TV) blood was also collected from the animals in experiment 2, which had been treated for 19 weeks, to determine intratesticular testosterone concentrations (Maddocks & Sharpe 1989). Rats were anaesthetised with halothane and heparinised by injection of 125 IU heparin (Leo Laboratories Ltd, Princes Risborough, Bucks, UK) into the left femoral vein.…”

Section: Collection Of Blood Samples and Testicular Interstitial Fluidmentioning

confidence: 99%

“…Rats were anaesthetised with halothane and heparinised by injection of 125 IU heparin (Leo Laboratories Ltd, Princes Risborough, Bucks, UK) into the left femoral vein. The right testis was exposed via a scrotal incision and TV blood collected into haematocrit tubes by puncturing the major surface testicular vein with a 28-gauge needle at a point just before its division into the mediastinal venous plexus at the anterior pole of the rete (Maddocks & Sharpe 1989).…”

Section: Collection Of Blood Samples and Testicular Interstitial Fluidmentioning

confidence: 99%

Effect of chronic administration of an aromatase inhibitor to adult male rats on pituitary and testicular function and fertility

Turner¹,

Morley²,

Atanassova³

et al. 2000

Journal of Endocrinology

107

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The aim of the present study was to evaluate the effects of the administration of a potent non-steroidal aromatase inhibitor, anastrozole, on male reproductive function in adult rats. As anastrozole was to be administered via the drinking water, a preliminary study was undertaken in female rats and showed that this route of administration was effective in causing a major decrease in uterine weight (P<0·02). In an initial study in male adult rats, anastrozole (100 mg/l or 400 mg/l) was administered via the drinking water for a period of 9 weeks. Treatment with either dose resulted in a significant increase (10%) in testis weight and increase in plasma FSH concentrations (P<0·01) throughout the 9 weeks. Mating was altered in both groups of anastrozole-treated rats, as they failed to produce copulatory plugs. Histological evaluation of the testes from anastrozole-treated rats revealed that spermatogenesis was grossly normal. In a more detailed study, adult rats were treated with 200 mg/l anastrozole via the drinking water for periods ranging from 2 weeks to 1 year. Plasma FSH and testosterone concentrations were increased significantly (P<0·001) during the first 19 weeks of treatment. However, LH concentrations were increased only at 19 weeks (P<0·001) in anastrozole-treated rats, and this coincided with a further increase in circulating and intratesticular testosterone concentrations (P<0·05). No consistent change in inhibin-B concentrations was observed during the study. Suppression of plasma oestradiol concentrations could not be demonstrated in anastrozole-treated animals, but oestradiol concentrations in testicular interstitial fluid were reduced by 18% (P<0·01). Mating was again inhibited by anastrozole treatment, but could be restored by s.c. injection of oestrogen, enabling demonstration that rats treated for 10 weeks or 9 months were still fertile. Testis weight was increased by 19% and 6% after treatment for 19 weeks and 1 year, respectively. Body weight was significantly decreased (P<0·01) by 19 weeks of anastrozole treatment; after 1 year the animals appeared to have less fat as indicated by a 27% decrease in the weight of the gonadal fat pad. The majority of anastrozole-treated animals had testes with normal spermatogenesis but, occasionally, seminiferous tubules showed abnormal loss of germ cells or contained only Sertoli cells. Ten percent of anastrozoletreated animals had testes that appeared to contain only Sertoli cells, and one rat had 'giant' testes in which the tubule lumens were severely dilated. Morphometric analysis of the normal testes at 19 weeks showed no difference in the number of Sertoli cells or germ cells, or the percentage volumes of the seminiferous epithelium, tubule lumens and interstitium between control and anastrozoletreated rats. On the basis of the present findings, oestrogen appears to be involved in the regulation of FSH secretion and testosterone production, and is also essential for normal mating behaviour in male rats. Furthermore, these data suggest that the br...

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

Cited by 27 publications

References 23 publications

Intratesticular Control Of Steroidogenesis

Intratesticular Control Of Steroidogenesis

The effects of FSH and of testosterone on the completion of meiosis and the very early steps of spermiogenesis of the rat: an in vitro study

Effect of chronic administration of an aromatase inhibitor to adult male rats on pituitary and testicular function and fertility

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