PMID- 9607803
OWN - NLM
STAT- MEDLINE
DCOM- 19980624
LR  - 20220318
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 139
IP  - 6
DP  - 1998 Jun
TI  - Expression and effect of insulin-like growth factor I on rat fetal Leydig cell 
      function and differentiation.
PG  - 2926-34
AB  - Insulin like growth factor I (IGF-I) is believed to be a potent para/autocrine 
      stimulator of Leydig cell function in adult testis. We investigated whether IGF-I 
      is also an intratesticular regulator of fetal Leydig cell function by measuring 
      its production in the fetal testis and its ability to affect testicular 
      steroidogenesis during fetal development. Northern blot analysis revealed one 
      major IGF-I transcript of 7-7.5 kb and two minor transcripts of 3.8 and 1.8 kb in 
      20.5 day fetal testis. IGF-I was detected by RIA in 16.5 fetal day testes, and 
      the amounts of IGF-I secreted by 16.5 and 20.5 fetal day testes in vitro were 
      much greater than the amounts contained in the testes, indicating active 
      synthesis in culture. The secretion of IGF-I by the fetal testis in vitro was 
      increased with testicular age and time in culture. It was not modified by 
      gonadotropins or (Bu)2cAMP. Testosterone secretion by fetal testes explanted 
      13.5, 16.5, 18.5, and 20.5 days after conception and cultured in the presence or 
      absence of 100 ng/ml LH for 3 days was not affected by the addition of 50 ng/ml 
      IGF-I to the medium. In contrast, the addition of IGF-I to dispersed fetal 
      testicular cells cultured for 3 days in the presence or absence of LH increased 
      the number of Leydig cells identified by a positive cytochemical reaction for 
      3beta-hydroxysteroid dehydrogenase (3betaHSD). This was more pronounced with 
      cells from 16.5- day-old fetuses (stage when the fetal Leydig cells are 
      differentiating in vivo) than with 20.5-day-old fetuses cells (stage when the 
      number and the function of fetal Leydig cells are stable or decreasing). It 
      results from both an increased differentiation of mesenchymal cells in fetal 
      Leydig cells and an increase in the mitotic index of the fetal Leydig cells, as 
      inferred from the small increase in the percentage of 
      bromodeoxyuridine/3betaHSD-positive cells. Both LH and IGF-I increased 
      significantly testosterone production by day 16.5 cells. In the presence of LH, a 
      high amount of testosterone was produced per 3betaHSD-positive cell; IGF-I 
      further increased this production. This effect was not observed with day 20.5 
      cells. The amounts of testosterone produced per 3betaHSD-positive cell cultured 
      in the presence of both LH and IGF-I were more than additive. Like IGF-I, insulin 
      (50 ng/ml) increased testosterone secretion per 3betaHSD-positive cells in 
      cultures of day 16.5 cells, but not in those of day 20.5, cells. Lastly, IGF-I 
      also increased the steroidogenic activity of each Leydig cell in cultures 
      containing (Bu)2cAMP, but its effects were weaker than those observed in the 
      presence of LH. This suggests that IGF-I has sites of action both upstream and 
      downstream cAMP generation. These results suggest that IGF-I acts as 
      paracrine/autocrine factor in the differentiation and activity of fetal Leydig 
      cells.
FAU - Rouiller-Fabre, V
AU  - Rouiller-Fabre V
AD  - INSERM-INRA U-418 and Universite Paris 7, France.
FAU - Lecref, L
AU  - Lecref L
FAU - Gautier, C
AU  - Gautier C
FAU - Saez, J M
AU  - Saez JM
FAU - Habert, R
AU  - Habert R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Insulin)
RN  - 3XMK78S47O (Testosterone)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 9002-67-9 (Luteinizing Hormone)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/drug effects/physiology
MH  - Cell Division/drug effects
MH  - Cells, Cultured
MH  - Fetus/cytology/*physiology
MH  - Insulin/pharmacology
MH  - Insulin-Like Growth Factor I/metabolism/pharmacology/*physiology
MH  - Leydig Cells/*cytology/*physiology
MH  - Luteinizing Hormone/pharmacology
MH  - Male
MH  - Rats/embryology
MH  - Rats, Wistar
MH  - Testis/embryology/metabolism
MH  - Testosterone/biosynthesis
EDAT- 1998/06/02 00:00
MHDA- 1998/06/02 00:01
CRDT- 1998/06/02 00:00
PHST- 1998/06/02 00:00 [pubmed]
PHST- 1998/06/02 00:01 [medline]
PHST- 1998/06/02 00:00 [entrez]
AID - 10.1210/endo.139.6.6035 [doi]
PST - ppublish
SO  - Endocrinology. 1998 Jun;139(6):2926-34. doi: 10.1210/endo.139.6.6035.