Effect of cryptorchidism on steroidogenic and mitogenic activities in rat testicular interstitial fluid

Risbridger, Gail P.; Drummond, Ann E.; Kerr, J. B.; Kretser, David Morritz de

doi:10.1530/jrf.0.0810617

Cited by 28 publications

(14 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with previous observations, peripheral testosterone levels were effectively normal in the bilaterally cryptorchid rats, as indicated by the seminal vesicle and thymus weights [40,41]. Testicular IF testosterone levels also appeared to be either normal or slightly elevated in the cryptorchid rat.…”

Section: Discussionsupporting

confidence: 90%

“…Testicular IF testosterone levels also appeared to be either normal or slightly elevated in the cryptorchid rat. Although similar results have been reported elsewhere [40,42], this latter observation was analyzed further because it was not consistent with previous results obtained in our laboratory and in some other laboratories using the same experimental model [41,43,44]. Continued synthesis of testosterone after testis collection, leading to artificially elevated testosterone levels in testicular IF, has been raised previously as a potential technical problem [45,46].…”

Section: Discussionmentioning

confidence: 52%

See 1 more Smart Citation

Local Regulation of Macrophage Subsets in the Adult Rat Testis: Examination of the Roles of the Seminiferous Tubules, Testosterone, and Macrophage-Migration Inhibitory Factor1

Meinhardt

Bacher²,

Metz³

et al. 1998

Biology of Reproduction

View full text Add to dashboard Cite

In the adult rat testis, macrophages belong to one of two subsets differentiated by expression or lack of expression of the resident macrophage surface antigen recognized by monoclonal antibody ED2. Local regulation of the testicular macrophage subsets was investigated in normal and 4-wk experimentally cryptorchid adult rats with and without s.c. testosterone implants (T-implants). Macrophage subsets ED2(+) (resident-type) and ED2(-) (monocyte-like) were identified immunohistochemically and counted in perfusion-fixed frozen testis sections. Depletion of the spermatogenic cells by cryptorchidism had no effect on testicular macrophage numbers. Inhibition of Leydig cell and seminiferous tubule function by low-dose (3 cm) T-implants caused a 40% reduction in ED2(+) resident macrophages in both scrotal and abdominal testes. High-dose (24 cm) T-implants, which inhibit Leydig cell function while maintaining normal seminiferous tubule function, also reduced the number of resident macrophages by approximately 40%, although this reduction was at least partially prevented in the abdominal testes. In the scrotal testis only, the ED2(-) monocyte/macrophage subset was significantly reduced in number by low-dose, but not high-dose, T-implants. The concentration of the Leydig cell-secreted cytokine macrophage-migration inhibitory factor (MIF) in testicular fluid was reduced by cryptorchidism, but not by the T-implants. When data from all experimental groups were combined, ED2(+) resident macrophage numbers showed a significant positive correlation with parameters of Leydig cell function (serum LH and testicular testosterone levels) but a negative correlation with MIF levels. This study indicates that Leydig cells regulate testicular macrophage numbers directly, rather than via an effect upon the seminiferous epithelium, in the adult rat testis. The data also suggest that testosterone and MIF play only a minor role, if any, in this regulation.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 52%

Local Regulation of Macrophage Subsets in the Adult Rat Testis: Examination of the Roles of the Seminiferous Tubules, Testosterone, and Macrophage-Migration Inhibitory Factor1

Meinhardt

Bacher²,

Metz³

et al. 1998

Biology of Reproduction

View full text Add to dashboard Cite

show abstract

“…Interstitial fluid (IF) collected from adult rats clearly contains mitogenic activity (Drummond et al, 1988;Risbridger et al, 1987;Ojeifo et al, 1990), but this activity is unchanged in the first 2 weeks after EDS treatment (when proliferation of LC precursors is occurring [see above]) or after experimental cryptorchidism (when LC hypertrophy is occurring, see above). Presumably, the mitogen present in adult testicular IF is different from that which exerts the effects just described during puberty, although no studies of mitogenic activity in IF collected from immature rats have been reported.…”

Section: Role Of Paracrine Factors In Lc Tumorigenesismentioning

confidence: 99%

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

View full text Add to dashboard Cite

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 ...

show abstract

“…Both changes can be averted by exogenous epidermal growth factor supplementation [26]. As a result of the diversity of putative growth factors and the difficulty in obtaining fractionated germ cells for culture, a number of groups have continued to utilize the mouse 3T3 fibroblast system in an easily performed bioassay that can distinguish differences in testicular mitogenic activity in a number of physiologic states, including vitamin A deficiency [28] and cryptorchidism [22].…”

Section: Discussionmentioning

confidence: 99%

Ontogeny of Rat Testicular Mitogenic Activity Studied with Transformed and Nontransformed Mouse 3T3 Fibroblasts

Searle

Pogach²,

Nathan³

et al. 1990

Archives of Andrology

View full text Add to dashboard Cite

The ontogeny of the testicular mitogenic activity of Sprague Dawley rats was evaluated by stimulation in vitro of [3H]thymidine uptake and cell number in Swiss 3T3 and transformed NIH 3T3 fibroblasts. Addition of various amounts of testicular cytosolic protein resulted in a dose-dependent increase in cell number in both cell lines. The [3H]thymidine responses to testicular cytosolic proteins was also dose dependent but in a nonparametric manner. In addition, the responses of 3T3 cells to testicular cytosol was apparently dependent on the developmental stage of the testis, the time of stimulation, and the proliferative nature of the fibroblast cell line. These results suggest the presence of multiple forms of mitogenic substance in testicular cytosol and imply that the relative amounts of these substances may depend on the age of the donor animal. These substances may be important in the proliferation or differentiation of cell types at various stages of testicular development.

show abstract

Effect of cryptorchidism on steroidogenic and mitogenic activities in rat testicular interstitial fluid

Cited by 28 publications

References 17 publications

Local Regulation of Macrophage Subsets in the Adult Rat Testis: Examination of the Roles of the Seminiferous Tubules, Testosterone, and Macrophage-Migration Inhibitory Factor1

Local Regulation of Macrophage Subsets in the Adult Rat Testis: Examination of the Roles of the Seminiferous Tubules, Testosterone, and Macrophage-Migration Inhibitory Factor1

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

Ontogeny of Rat Testicular Mitogenic Activity Studied with Transformed and Nontransformed Mouse 3T3 Fibroblasts

Contact Info

Product

Resources

About