Gubernacular cell division in different rodent models of cryptorchidism supports indirect androgenic action via the genitofemoral nerve.
OBJECTIVE
The role of the "gubernaculum" in testicular descent remains controversial. Androgens are proposed to act indirectly by the genitofemoral nerve (GFN) releasing calcitonin gene-related peptide. The authors studied the effects of sensory nerve ablation and androgen blockade on mitosis in the gubernacular tip to determine whether androgens act directly or indirectly.


METHODS
Five rat models were examined for bromodeoxyuridine (BUdR)-labeling: (i) Sprague-Dawley (SD) rats (controls), (ii) prenatal flutamide-treated rats (75 mg/kg to dams on D16-19 gestation), (iii) neonatal capsaicin-treated rats (50 mg/kg, subcutaneous on day 0), (iv) congenitally cryptorchid transcrotal (TS) rats, and (v) capsaicin-treated TS rats (50 mg/kg, subcutaneous on day 0). Newborn rats were collected at days 0, 2, 4, 6, 8, and 10 (age, n = 5/model, n = 30) and were injected intraperitoneally with 1 mg/kg BUdR, 2 hours before killing. Histological sections of gubernaculum were examined immunohistochemically for BUdR labeling.


RESULTS
In SD (control) rats, DNA synthesis in the gubernacular tip was high at birth, reached a peak at day 2, and then decreased progressively until day 10. A similar pattern was observed in TS rats. However, quantitatively, the levels were significantly higher. In flutamide-treated rats, DNA synthesis was suppressed until day 6, similar suppression was observed in capsaicin-treated SD, and TS rats until day 4.


CONCLUSIONS
Flutamide, a competitive androgen receptor blocker, reduces gubernacular mitosis to basal levels until day 6, highlighting the importance of androgen receptor. Excess DNA accumulation in TS rats is consistent with the known excess of GFN fibers and calcitonin gene-related peptide in this mutant. Capsaicin-inhibited mitosis in both day 2 SD and TS rats suggests that the GFN mediates androgen action on early postnatal gubernacular DNA synthesis and growth.
Ng
Sunt Li
SL
F. Douglas Stephens Surgical Research Laboratory, Murdoch Children's Research Institute, Parkville, Victoria, 3052, Australia.
Bidarkar
Sandeep S
SS
Sourial
Magdy
M
Farmer
Pamela J
PJ
Donath
Susan
S
Hutson
John M
JM
D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000633:toxicity*; D000728:Androgens / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis; D002211:Capsaicin / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D003456:Cryptorchidism / Q000139:chemically induced / Q000503:physiopathology*; D004247:DNA / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D005267:Femoral Nerve / Q000187:drug effects / Q000502:physiology*; D005485:Flutamide / Q000633:toxicity*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects* / Q000378:metabolism
D000726:Androgen Antagonists; D000728:Androgens; D005485:Flutamide; D004247:DNA; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin