| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Minireview |
a Departments of Comparative Medicine
b Animal Science, The University of Tennessee College of Veterinary Medicine, Knoxville, Tennessee 37996
Five main cell types are present in the Leydig cell lineage, namely the mesenchymal precursor cells, progenitor cells, newly formed adult Leydig cells, immature Leydig cells, and mature Leydig cells. Peritubular mesenchymal cells are the precursors to Leydig cells at the onset of Leydig cell differentiation in the prepubertal rat as well as in the adult rat during repopulation of the testis interstitium after ethane dimethane sulfonate (EDS) treatment. Leydig cell differentiation cannot be viewed as a simple process with two distinct phases as previously reported, simply because precursor cell differentiation and Leydig cell mitosis occur concurrently. During development, mesenchymal and Leydig cell numbers increase linearly with an approximate ratio of 1:2, respectively. The onset of precursor cell differentiation into progenitor cells is independent of LH; however, LH is essential for the later stages in the Leydig cell lineage to induce cell proliferation, hypertrophy, and establish the full organelle complement required for the steroidogenic function. Testosterone and estrogen are inhibitory to the onset of precursor cell differentiation, and these hormones produced by the mature Leydig cells may be of importance to inhibit further differentiation of precursor cells to Leydig cells in the adult testis to maintain a constant number of Leydig cells. Once the progenitor cells are formed, androgens are essential for the progenitor cells to differentiate into mature adult Leydig cells. Although early studies have suggested that FSH is required for the differentiation of Leydig cells, more recent studies have shown that FSH is not required in this process. Anti-Müllerian hormone has been suggested as a negative regulator in Leydig cell differentiation, and this concept needs to be further explored to confirm its validity. Insulin-like growth factor I (IGF-I) induces proliferation of immature Leydig cells and is associated with the promotion of the maturation of the immature Leydig cells into mature adult Leydig cells. Transforming growth factor 
(TGF) is a mitogen for mesenchymal precursor cells. Moreover, both TGF and TGFß (to a lesser extent than TGF) stimulate mitosis in Leydig cells in the presence of LH (or hCG). Platelet-derived growth factor-A is an essential factor for the differentiation of adult Leydig cells; however, details of its participation are still not known. Some cytokines secreted by the testicular macrophages are mitogenic to Leydig cells. Moreover, retarded or absence of Leydig cell development has been observed in experimental models with impaired macrophage function. Thyroid hormone is critical to trigger the onset of mesenchymal precursor cell differentiation into Leydig progenitor cells, proliferation of mesenchymal precursors, acceleration of the differentiation of mesenchymal cells into Leydig cell progenitors, and enhance the proliferation of newly formed Leydig cells in the neonatal and EDS-treated adult rat testes.
1 Supported by grants from UT-COE R180101-08 and Professional Development Awards Program.
2 Correspondence. FAX: 865 974 2215; mendisc{at}utk.edu
This article has been cited by other articles:
|
|
 |
|
  I. Qamar, E. Park, E.-Y. Gong, H. J. Lee, and K. Lee ARR19 (Androgen Receptor Corepressor of 19 kDa), an Antisteroidogenic Factor, Is Regulated by GATA-1 in Testicular Leydig Cells J. Biol. Chem., July 3, 2009; 284(27): 18021 - 18032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Allan, P. Lim, M. Robson, J. Spaliviero, and D. J. Handelsman Transgenic mutant D567G but not wild-type human FSH receptor overexpression provides FSH-independent and promiscuous glycoprotein hormone Sertoli cell signaling Am J Physiol Endocrinol Metab, May 1, 2009; 296(5): E1022 - E1028. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.-S. Wang, S. Yeh, C.-R. Tzeng, and C. Chang Androgen Receptor Roles in Spermatogenesis and Fertility: Lessons from Testicular Cell-Specific Androgen Receptor Knockout Mice Endocr. Rev., April 1, 2009; 30(2): 119 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Rijntjes, H. J. M. Swarts, R. Anand-Ivell, and K. J. Teerds Prenatal induced chronic dietary hypothyroidism delays but does not block adult-type Leydig cell development Am J Physiol Endocrinol Metab, February 1, 2009; 296(2): E305 - E314. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Wagner, S. M. Wajner, and A. L. Maia The role of thyroid hormone in testicular development and function J. Endocrinol., December 1, 2008; 199(3): 351 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Rijntjes, A. T. Wientjes, H. J. M. Swarts, D. G. de Rooij, and K. J. Teerds Dietary-Induced Hyperthyroidism Marginally Affects Neonatal Testicular Development J Androl, November 1, 2008; 29(6): 643 - 653. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Takenaka, M. Yagi, K. Amakasu, K. Suzuki, and H. Suzuki Retarded Differentiation of Leydig Cells and Increased Apoptosis of Germ Cells in the Initial Round of Spermatogenesis of Rats With Lethal Dwarf and Epilepsy (lde/lde) Phenotypes J Androl, November 1, 2008; 29(6): 669 - 678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Culty, R. Thuillier, W. Li, Y. Wang, D. B. Martinez-Arguelles, C. G. Benjamin, K. M. Triantafilou, B. R. Zirkin, and V. Papadopoulos In Utero Exposure to Di-(2-ethylhexyl) Phthalate Exerts Both Short-Term and Long-Lasting Suppressive Effects on Testosterone Production in the Rat Biol Reprod, June 1, 2008; 78(6): 1018 - 1028. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J Teerds, E. Rijntjes, M. B Veldhuizen-Tsoerkan, F. F G Rommerts, and M. de Boer-Brouwer The development of rat Leydig cell progenitors in vitro: how essential is luteinising hormone? J. Endocrinol., September 1, 2007; 194(3): 579 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Shiraishi and M. Ascoli Lutropin/Choriogonadotropin Stimulate the Proliferation of Primary Cultures of Rat Leydig Cells through a Pathway that Involves Activation of the Extracellularly Regulated Kinase 1/2 Cascade Endocrinology, July 1, 2007; 148(7): 3214 - 3225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-J. He, M. Hirata, N. Yamauchi, S. Hashimoto, and M.-a. Hattori The disruption of circadian clockwork in differentiating cells from rat reproductive tissues as identified by in vitro real-time monitoring system J. Endocrinol., June 1, 2007; 193(3): 413 - 420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Fombonne, C. Charrier, I. Goddard, E. Moyse, and S. Krantic Leptin-Mediated Decrease of Cyclin A2 and Increase of Cyclin D1 Expression: Relevance for the Control of Prepubertal Rat Leydig Cell Division and Differentiation Endocrinology, May 1, 2007; 148(5): 2126 - 2137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S M L C Mendis-Handagama, H B S Ariyaratne, L Mrkonjich, and R Ivell Expression of insulin-like peptide 3 in the postnatal rat Leydig cell lineage: timing and effects of triiodothyronine-treatment Reproduction, February 1, 2007; 133(2): 479 - 485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. de Montgolfier, J. Dufresne, M. Letourneau, J. J. Nagler, A. Fournier, C. Audet, and D. G. Cyr The Expression of Multiple Connexins Throughout Spermatogenesis in the Rainbow Trout Testis Suggests a Role for Complex Intercellular Communication Biol Reprod, January 1, 2007; 76(1): 2 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. N Kahiri, M W. Khalil, F. Tekpetey, and G. M Kidder Leydig cell function in mice lacking connexin43. Reproduction, October 1, 2006; 132(4): 607 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E T Bagu, S Cook, C L Gratton, and N C Rawlings Postnatal changes in testicular gonadotropin receptors, serum gonadotropin, and testosterone concentrations and functional development of the testes in bulls. Reproduction, September 1, 2006; 132(3): 403 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. Franca, M. O. Suescun, J. R. Miranda, A. Giovambattista, M. Perello, E. Spinedi, and R. S. Calandra Testis Structure and Function in a Nongenetic Hyperadipose Rat Model at Prepubertal and Adult Ages Endocrinology, March 1, 2006; 147(3): 1556 - 1563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.-S. Ge, Q. Dong, C. M. Sottas, V. Papadopoulos, B. R. Zirkin, and M. P. Hardy In search of rat stem Leydig cells: Identification, isolation, and lineage-specific development PNAS, February 21, 2006; 103(8): 2719 - 2724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. Schulz, S. Menting, J. Bogerd, L. R. Franca, D. A.R. Vilela, and H. P. Godinho Sertoli Cell Proliferation in the Adult Testis--Evidence from Two Fish Species Belonging to Different Orders Biol Reprod, November 1, 2005; 73(5): 891 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P.A. van Bragt, N. Ciliberti, W. L. Stanford, D. G. de Rooij, and A. M.M. van Pelt LY6A/E (SCA-1) Expression in the Mouse Testis Biol Reprod, October 1, 2005; 73(4): 634 - 638. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. De Gendt, N. Atanassova, K. A. L. Tan, L. R. de Franca, G. G. Parreira, C. McKinnell, R. M. Sharpe, P. T. K. Saunders, J. I. Mason, S. Hartung, et al. Development and Function of the Adult Generation of Leydig Cells in Mice with Sertoli Cell-Selective or Total Ablation of the Androgen Receptor Endocrinology, September 1, 2005; 146(9): 4117 - 4126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Davidoff, R. Middendorff, G. Enikolopov, D. Riethmacher, A. F. Holstein, and D. Muller Progenitor cells of the testosterone-producing Leydig cells revealed J. Cell Biol., December 6, 2004; 167(5): 935 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.M. Lei, S. Mishra, P. Ponnuru, X. Li, Z.W. Yang, and Ch.V. Rao Testicular Phenotype in Luteinizing Hormone Receptor Knockout Animals and the Effect of Testosterone Replacement Therapy Biol Reprod, November 1, 2004; 71(5): 1605 - 1613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Ramaswamy, C R Pohl, G R Marshall, and T M Plant A switch from continuous to episodic testicular testosterone release in response to pulsatile LH stimulation in juvenile rhesus monkeys (Macaca mulatta) J. Endocrinol., October 1, 2004; 183(1): 61 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hombach-Klonisch, J. Schon, A. Kehlen, S. Blottner, and T. Klonisch Seasonal Expression of INSL3 and Lgr8/Insl3 Receptor Transcripts Indicates Variable Differentiation of Leydig Cells in the Roe Deer Testis Biol Reprod, October 1, 2004; 71(4): 1079 - 1087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. de Rooij and M. P. A. van Bragt Leydig Cells: Testicular Side Population Harbors Transplantable Leydig Stem Cells Endocrinology, September 1, 2004; 145(9): 4009 - 4010. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Schmahl, Y. Kim, J. S. Colvin, D. M. Ornitz, and B. Capel Fgf9 induces proliferation and nuclear localization of FGFR2 in Sertoli precursors during male sex determination Development, August 1, 2004; 131(15): 3627 - 3636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Suzuki, M. Yagi, K. Saito, and K. Suzuki Dysplastic Development of Seminiferous Tubules and Interstitial Tissue in Rat Hypogonadic (hgn/hgn) Testes Biol Reprod, July 1, 2004; 71(1): 104 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.M. Ben Saad and D.L. Maurel Reciprocal Interaction Between Seasonal Testis and Thyroid Activity in Zembra Island Wild Rabbits (Oryctolagus cuniculus): Effects of Castration, Thyroidectomy, Temperature, and Photoperiod Biol Reprod, April 1, 2004; 70(4): 1001 - 1009. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-F. Lee, W. S.B. Yeung, J. F.C. Chow, C. K. Shum, and J. M. Luk Different Testicular Gene Expression Patterns in the First Spermatogenic Cycle of Postnatal and Vitamin A-Deficient Rat Testis Biol Reprod, April 1, 2004; 70(4): 1010 - 1017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.-p. Zhang, T. Pakarainen, F. Zhu, M. Poutanen, and I. Huhtaniemi Molecular Characterization of Postnatal Development of Testicular Steroidogenesis in Luteinizing Hormone Receptor Knockout Mice Endocrinology, March 1, 2004; 145(3): 1453 - 1463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ivell, M. Balvers, R. J. K. Anand, H.-J. Paust, C. McKinnell, and R. Sharpe Differentiation-Dependent Expression of 17{beta}-Hydroxysteroid Dehydrogenase, Type 10, in the Rodent Testis: Effect of Aging in Leydig Cells Endocrinology, July 1, 2003; 144(7): 3130 - 3137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Walch, E. Clavarino, and P. L. Morris Prostaglandin (PG) FP and EP1 Receptors Mediate PGF2{alpha} and PGE2 Regulation of Interleukin-1{beta} Expression in Leydig Cell Progenitors Endocrinology, April 1, 2003; 144(4): 1284 - 1291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xu, A. R. Beyer, W. H. Walker, and E. A. McGee Developmental and Stage-Specific Expression of Smad2 and Smad3 in Rat Testis J Androl, March 1, 2003; 24(2): 192 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Pizzagalli, B. Hagenbuch, B. Stieger, U. Klenk, G. Folkers, and P. J. Meier Identification of a Novel Human Organic Anion Transporting Polypeptide as a High Affinity Thyroxine Transporter Mol. Endocrinol., October 1, 2002; 16(10): 2283 - 2296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Walch and P. L. Morris Cyclooxygenase 2 Pathway Mediates IL-1{beta} Regulation of IL-1{alpha}, -1{beta}, and IL-6 mRNA Levels in Leydig Cell Progenitors Endocrinology, September 1, 2002; 143(9): 3276 - 3283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-J. Chen, Y. Lukyanenko, and J. C. Hutson 25-Hydroxycholesterol Is Produced by Testicular Macrophages During the Early Postnatal Period and Influences Differentiation of Leydig Cells In Vitro Biol Reprod, May 1, 2002; 66(5): 1336 - 1341. [Abstract] [Full Text]
|
|
|
|
 |
|
 P. J. O'Shaughnessy, H. Johnston, L. Willerton, and P. J. Baker Failure of normal adult Leydig cell development in androgen-receptor-deficient mice J. Cell Sci., January 9, 2002; 115(17): 3491 - 3496. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
