PMID- 17442358
OWN - NLM
STAT- MEDLINE
DCOM- 20070813
LR  - 20131121
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 221
IP  - 1
DP  - 2007 May 15
TI  - Lonidamine affects testicular steroid hormones in immature mice.
PG  - 95-101
AB  - The effects on the hypothalamus-pituitary-testicular axis of the well-known 
      antispermatogenic drug lonidamine (LND) has not been elucidated so far. In the 
      present study, the possible changes of the testicular steroid hormones were 
      evaluated in immature mice for a better characterization of the LND adverse 
      effects both in its use as antitumoral agent and male contraceptive. Male CD1 
      mice were orally treated on postnatal day 28 (PND28) with LND single doses (0 or 
      100 mg/kg b.w.) and euthanized every 24 h from PND29 to PND32, on PND35 and on 
      PND42 (1 and 2 weeks after the administration, respectively). Severe testicular 
      effects were evidenced in the LND treated groups, including: a) significant 
      testis weight increase, 24 h and 48 h after dosing; b) sperm head counts decrease 
      (more than 50% of the control) on PND29-32; c) damage of the tubule morphology 
      primarily on the Sertoli cell structure and germ cell exfoliation. All these 
      reproductive endpoints were recovered on PND42. At the same time, a significant 
      impairment of the testicular steroid balance was observed in the treated mice, as 
      evidenced by the decrease of testosterone (T) and androstenedione (ADIONE) and 
      the increase of 17OH-progesterone (17OH-P4) on the first days after dosing, while 
      the testicular content of 17beta-estradiol (E2) was unchanged. The hormonal 
      balance was not completely restored afterwards, as levels of T, ADIONE and 
      17OH-P4 tended to be higher in the treated mice than in the controls, on PND35 
      and PND42. These data showed for the first time that LND affects intratesticular 
      steroids in experimental animals. However further data are needed both to 
      elucidate the mechanism responsible for the impairment of these metabolic 
      pathways and to understand if the androgens decrease observed after LND 
      administration could be partially involved in the testicular damage.
FAU - Traina, Maria Elsa
AU  - Traina ME
AD  - Department of Drug Research and Evaluation, Istituto Superiore di Sanita, Viale 
      Regina Elena, 299. 00161 Rome, Italy. Traina@iss.it
FAU - Guarino, Maria
AU  - Guarino M
FAU - Natoli, Alessia
AU  - Natoli A
FAU - Romeo, Antonella
AU  - Romeo A
FAU - Urbani, Elisabetta
AU  - Urbani E
LA  - eng
PT  - Journal Article
DEP - 20070418
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Antispermatogenic Agents)
RN  - 0 (Hydroxyprogesterones)
RN  - 0 (Indazoles)
RN  - 0 (Testicular Hormones)
RN  - 3XMK78S47O (Testosterone)
RN  - 409J2J96VR (Androstenedione)
RN  - 4TI98Z838E (Estradiol)
RN  - U78804BIDR (lonidamine)
SB  - IM
MH  - Age Factors
MH  - Androstenedione/metabolism
MH  - Animals
MH  - Antispermatogenic Agents/administration & dosage/toxicity
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Estradiol/metabolism
MH  - Hydroxyprogesterones/metabolism
MH  - Indazoles/administration & dosage/*toxicity
MH  - Intubation, Gastrointestinal
MH  - Male
MH  - Mice
MH  - Microscopy, Polarization
MH  - Organ Size/drug effects
MH  - Seminiferous Tubules/drug effects/pathology
MH  - Sertoli Cells/drug effects/pathology
MH  - Sperm Count
MH  - Spermatogenesis/drug effects
MH  - Spermatozoa/drug effects/pathology
MH  - Testicular Hormones/*metabolism
MH  - Testis/*drug effects/metabolism/pathology
MH  - Testosterone/metabolism
MH  - Time Factors
EDAT- 2007/04/20 09:00
MHDA- 2007/08/19 09:00
CRDT- 2007/04/20 09:00
PHST- 2006/01/05 00:00 [received]
PHST- 2006/12/01 00:00 [revised]
PHST- 2007/01/21 00:00 [accepted]
PHST- 2007/04/20 09:00 [pubmed]
PHST- 2007/08/19 09:00 [medline]
PHST- 2007/04/20 09:00 [entrez]
AID - S0041-008X(07)00038-5 [pii]
AID - 10.1016/j.taap.2007.01.028 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2007 May 15;221(1):95-101. doi: 
      10.1016/j.taap.2007.01.028. Epub 2007 Apr 18.