PMID- 15816370
OWN - NLM
STAT- MEDLINE
DCOM- 20050711
LR  - 20191026
IS  - 0391-4097 (Print)
IS  - 0391-4097 (Linking)
VI  - 28
IP  - 1
DP  - 2005 Jan
TI  - Hyperprolactinemia affects spermiogenesis in adult male rats.
PG  - 39-48
AB  - The mechanisms underlying the antifertility effects of hyperprolactinemia have 
      yet to be established in an appropriate experimental model. Hyperprolactinemia is 
      a known side effect of fluphenazine, a broad spectrum, long-acting phenothiazine 
      known to be dopamine type-D2 receptor antagonist. In our earlier study in adult 
      male rats, we reported that fluphenazine at a dose of 3 mg/kg/day suppressed 
      serum FSH but not testosterone (T) through increasing dopamine (DA) metabolism in 
      the pituitary gland, within 60 days. Fluphenazine treatment affected sperm 
      quality and male rats treated with fluphenazine sired fewer litters. The effects 
      of fluphenazine-induced hyperprolactinemia on sperm quality appeared to be 
      related to reduced FSH. We now report that FSH suppression enhanced the uptake of 
      acridine orange (AO), a DNA intercalating, fluorescent dye by the 
      fluphenazine-treated caput epididymal sperms with concomitant reduction in the 
      uptake of thiol-specific monobromobimane (mBBr) fluorescent dye in vitro, 
      suggesting greater accessibility of DNA intercalating dye to sperm chromatin and 
      reduction in free sperm protein thiols. The concomitant increase in AO and 
      decrease in mBBr fluorescence was suggestive of loose chromatin packaging in 
      caput epididymal sperms after treatment with fluphenazine at 3 mg/kg/day for 60 
      days. The suppression in levels of protamine (P1) in caput epididymal sperms 
      suggested that chromatin hypocompaction was due to reduced deposition of 
      protamines in sperm chromatin. Reduction in testicular levels of cyclic adenosyl 
      3', 5' monophosphate response element modulator (CREMtau) and P1 further 
      suggested that reduced deposition was indeed due to reduced synthesis. The 
      concomitant reduction in testicular levels of transition protein 1 (TP1) and 
      transition protein 2 (TP2) also suggested that hypoprotamination was due to 
      reduced synthesis of these proteins crucial for facilitating P1 deposition. The 
      effect appeared to have occurred at the level of translation of CREMtau, since 
      its transcript levels were unaffected whereas those of TP1, TP2 and P1 and 
      protamine were upregulated. The study led to the view that the effects of FSH 
      suppression were manifest on the posttranscriptional modifications of CREMtau, as 
      also on transcript repression of TP1, TP2, P1, which do the RNA- binding proteins 
      bring about. Reduction in FSH did not decrease ABP expression in the testis, 
      which has recently been implicated in the expression of transition protein 1 in 
      vitro. However, a significant reduction was evident after fluphenazine treatment, 
      in the immunoexpression of testicular cAMP, the mediator of FSH effects in the 
      Sertoli cells and putative mediator of ABP effects in the spermatids. The study 
      suggests that fluphenazine-induced hyperprolactinemia suppressed FSH and affected 
      a putative cAMP-dependent mechanism underlying posttranscriptional modification 
      of spermatidal genes involved in chromatin condensation, presumably by reducing 
      the availability/secretion of ABP, a paracrine regulator of spermiogenesis in 
      vitro.
FAU - Aleem, M
AU  - Aleem M
AD  - Department of Urology, Medical College of Ohio, Toledo, Ohio, USA.
FAU - Choudhari, J
AU  - Choudhari J
FAU - Padwal, V
AU  - Padwal V
FAU - Balasinor, N
AU  - Balasinor N
FAU - Parte, P
AU  - Parte P
FAU - Gill-Sharma, M K
AU  - Gill-Sharma MK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - J Endocrinol Invest
JT  - Journal of endocrinological investigation
JID - 7806594
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Protamines)
RN  - 0 (Sulfhydryl Compounds)
RN  - 0 (Transcription Factors)
RN  - 0 (spermatid transition proteins)
RN  - 135844-64-3 (Cyclic AMP Response Element Modulator)
RN  - E0399OZS9N (Cyclic AMP)
RN  - S79426A41Z (Fluphenazine)
SB  - IM
MH  - Animals
MH  - Antipsychotic Agents
MH  - Blotting, Western
MH  - Chromosomal Proteins, Non-Histone/blood
MH  - Cyclic AMP/metabolism
MH  - Cyclic AMP Response Element Modulator
MH  - DNA-Binding Proteins/blood
MH  - Fluphenazine
MH  - Gene Expression/drug effects
MH  - Hyperprolactinemia/chemically induced/*physiopathology
MH  - Male
MH  - Protamines/blood
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sex Chromatin/metabolism
MH  - Spermatogenesis/*physiology
MH  - Spermatozoa/drug effects/metabolism
MH  - Sulfhydryl Compounds/metabolism
MH  - Testis/drug effects/metabolism
MH  - Transcription Factors/blood
EDAT- 2005/04/09 09:00
MHDA- 2005/07/12 09:00
CRDT- 2005/04/09 09:00
PHST- 2005/04/09 09:00 [pubmed]
PHST- 2005/07/12 09:00 [medline]
PHST- 2005/04/09 09:00 [entrez]
AID - 2905 [pii]
AID - 10.1007/BF03345528 [doi]
PST - ppublish
SO  - J Endocrinol Invest. 2005 Jan;28(1):39-48. doi: 10.1007/BF03345528.