Development of Leydig Cells in the Insulin-Like Growth Factor-I (IGF-I) Knockout Mouse: Effects of IGF-I Replacement and Gonadotropic Stimulation

• Published in: Biology of reproduction Vol. 70; no. 3; pp. 632 - 639
• Main Authors: Wang, Guimin, Hardy, Matthew P
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction 01-03-2004
• Subjects: Animals; Biological and medical sciences; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Division - drug effects; Cell Division - physiology; Cell Lineage - drug effects; Cell Lineage - physiology; Fundamental and applied biological sciences. Psychology; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - pharmacology; Leydig Cells - cytology; Leydig Cells - drug effects; Luteinizing Hormone - blood; Luteinizing Hormone - pharmacology; Male; Mammalian male genital system; Mice; Mice, Inbred Strains; Mice, Knockout; Morphology. Physiology; Sexual Maturation; Testosterone - blood; Vertebrates: reproduction; Vertebrata; Reproduction; Mammalia; Mouse; Animal; Rodentia; Development; Mutation; Testicle; Insulin like growth factor 1; Male genital system; Leydig cell
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.103.022590

Targeted gene deletion of insulin-like growth factor-I (IGF-I) results in diminished numbers of Leydig cells (LCs) and lower
circulating testosterone (T) levels in adult males. The impact of endogenous IGF-I withdrawal on proliferation (labeling index,
LI) and differentiation of LCs was investigated, testing for restorative effects of IGF-I replacement and/or LH stimulation.
With IGF-I replacement in mutant mice, LIs increased more than 200% ( P < 0.05). LC numbers were also increased by 200%, whereas the numbers of intermediate cell progenitors (PLCs) were unchanged
compared to mutant vehicle controls. LIs of PLCs in wild-type males increased by 200% after LH stimulation, and LC numbers
increased by 50% compared to vehicle-treated controls ( P < 0.05). In contrast, there was no effect of LH on LI in mutant mice, but LC numbers still increased by 30% ( P < 0.05). Additive effects on LI and cell numbers were observed in response to IGF-I plus LH in mutants, implying that the
two hormones use separate signaling pathways. Serum T and LH levels in wild-type and mutant males were equivalent. Exogenous
LH increased T production 8-fold in wild-type males ( P < 0.01). In mutant mice, neither LH stimulation nor IGF-I alone affected serum T levels, but IGF-I plus LH stimulation increased
serum T 2-fold ( P < 0.05). These data support the conclusions that 1) IGF-I is a critical autocrine and/or paracrine factor in the control
of adult LC numbers and function; and 2) LH is not a direct mitogenic factor for LCs, and acts in part through IGF-I to stimulate
proliferative activity.