Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P01178 (
oxytocin
)
15,767
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Oxytocin
and its receptor are present in the mammalian prostate, and the peptide has been shown to increase prostatic growth,
5alpha-reductase
activity, and contractility. This study was performed to investigate whether local concentrations of the peptide were regulated by gonadal steroids in order to establish whether
oxytocin
has a physiological role in the prostate. Both intact and castrated adult Wistar rats were treated daily for 7 days with either testosterone propionate or the antiandrogen cyproterone acetate. Animals were then killed, and plasma hormone and prostatic
oxytocin
concentrations were measured. A separate group of rats was treated with the
5alpha-reductase
inhibitor finasteride to investigate whether testosterone or dihydrotestosterone (DHT) was involved in regulating
oxytocin
concentrations. In a further series of experiments, rats were treated with diethylstilbestrol (DES) or the antiestrogen tamoxifen. Treatment with testosterone significantly decreased prostatic
oxytocin
, whereas reduction of androgens by castration or by administration of cyproterone acetate increased prostatic peptide concentrations without altering circulating levels of the peptide. Treatment with finasteride increased plasma testosterone but decreased DHT concentrations. Prostatic
oxytocin
concentrations were higher in finasteride-treated animals than in control animals with comparable testosterone levels. The data suggest that both testosterone and DHT are capable of decreasing prostatic
oxytocin
concentrations. Treatment with DES did not significantly alter prostatic
oxytocin
, but administration of tamoxifen decreased concentrations of the peptide, suggesting that low levels of estrogen may be necessary for
oxytocin
production. These data provide evidence that
oxytocin
is regulated by androgens, and we hypothesize that this regulatory mechanism may be involved in controlling prostatic growth.
...
PMID:Evidence for the regulation of prostatic oxytocin by gonadal steroids in the rat. 1010 Apr 77
Many molecules, including steroid and peptide hormones, prostaglandins and cytokines, regulate the preparation, initiation and progression of parturition in mammals. Gene targeting studies show that, in the knockout mice of
steroid 5alpha-reductase
type 1 gene, prostaglandin F2alpha receptor gene and cytosolic phospholipase A2 gene, parturition was severely disturbed, although live offspring were delivered by Caesarean section. Relaxin gene-disrupted mice also showed protracted labour. However, most knockout mice in which the steroid hormone, prostaglandin, cytokine or peptide hormone (for example,
oxytocin
, corticotrophin releasing hormone and endothelin) endocrine-paracrine systems are disrupted are inadequate for analysis of the mechanism of parturition because they die before reaching reproductive age or are infertile, or because they reproduce normally. A conditional knockout strategy, for example, using the Cre-LoxP system, should be considered for investigating the biochemical background of parturition to overcome these problems.
...
PMID:What knockout mice can tell us about parturition. 1035 94
Oxytocin
(OT) is present in the male reproductive tract, where it is known to modulate contractility, cell growth, and steroidogenesis. Little is known about how OT regulates these processes. This study describes the localization of OT receptor in the rat ventral prostate and investigates if OT regulates gene expression and/or activity of
5alpha-reductase
isoforms I and II. The ventral prostates of adult male Wistar rats were collected following daily sc administration of saline (control), OT, a specific OT antagonist or both OT plus antagonist for 3 d. Expression of the OT receptor was identified in the ventral prostate by RT-PCR and Western blot, and confirmed to be a single active binding site by radioreceptor assay. Immunohistochemistry localized the receptor to the epithelium of prostatic acini and to the stromal tissue. Real-time RT-PCR determined that OT treatment significantly reduced expression of
5alpha-reductase
I but significantly increased
5alpha-reductase
II expression in the ventral prostate. Activity of both isoforms of
5alpha-reductase
was significantly increased by OT, resulting in increased concentration of prostatic dihydrotestosterone. In conclusion, OT is involved in regulating conversion of testosterone to the biologically active dihydrotestosterone in the rat ventral prostate. It does so by differential regulation of
5alpha-reductase
isoforms I and II.
...
PMID:Regulation of 5alpha-reductase isoforms by oxytocin in the rat ventral prostate. 1535 76
Benign prostatic hyperplasia (BPH) is a leading disorder of the elderly male population that is characterised by a progressive enlargement of prostatic tissue, resulting in obstruction of the proximal urethra and causing urinary flow disturbances. The pathophysiology of BPH associated with lower urinary tract symptoms is characterised by increased adrenergic tone (dynamic component) leading to smooth muscle contraction and prostatic overgrowth due to androgenic stimulation (static component); therefore, the therapeutic armamentarium of BPH can be broadly divided into antiadrenergic and antiandrogenic approaches. alpha1-Adrenoceptor antagonists and
5alpha-reductase
inhibitors are well-established representatives of the two categories, respectively. Other antiandrogenic approaches involve gonadotropin-releasing hormone agonists and antagonists for the treatment of prostate hyperplasia. Apart from these approaches, new approaches with novel targets are emerging. The advent of new therapies is, however, more oriented towards the static component. These involve metabolic factors (hexokinase inhibitor), growth factors (vitamin D3 analogues),
oxytocin
antagonists and gonadotropin-releasing hormone Gi agonist-based therapies. Gene therapy and photodynamic therapies are other emerging therapies for relieving symptoms in BPH patients. With the initial success of upcoming targets, the unmet need to develop an efficacious and relatively safe therapeutic modality is discussed. Nevertheless, their long-term safety and efficacy needs to be evaluated in large-scale clinical trials. The future also belongs to combination therapies to combat both dynamic and static disease components and for extended indications such as micturition disorder and non-bacterial prostatitis.
...
PMID:Benign prostatic hyperplasia: an insight into current investigational medical therapies. 1625 76
Oxytocin
(OT) is traditionally thought of as a "female" neurohypophysis hormone due to its role in parturition and milk ejection. However, OT is recognized as having endocrine and paracrine roles in male reproduction. At ejaculation, a burst of OT is released from the neurohypophysis into the systemic circulation and stimulates contractions of the reproductive tract aiding sperm release. There is conclusive evidence that OT is synthesized within the mammalian testis, epididymis and prostate and the presence of OT receptors (OTRs) through the reproductive tract supports a local action for this peptide. OT has a paracrine role in stimulating contractility of the seminiferous tubules, epididymis and the prostate gland. Interestingly, OT has also been shown to modulate androgen levels in these tissues via stimulation of the conversion of testosterone to dihydrotestostone (DHT) by
5alpha-reductase
. The elucidation of OT's role in male reproduction has suggested a number of potential therapeutic uses for this hormone. Exogenous administration of OT has, in some cases, been shown to increase the numbers of ejaculated sperm, possibly by stimulating contractions of the reproductive tract and thus aiding sperm passage. Within the prostate, OT has been shown to affect gland growth both directly and via its interaction with androgen metabolism. Prostate pathologies due to unregulated cell proliferation/growth, such as benign prostatic hyperplasia and cancer, are unfortunately very common and few effective treatments are available. Greater understanding of paracrine growth mediators, such as OT, is likely to provide new mechanisms for treating such pathologies.
...
PMID:Oxytocin--its role in male reproduction and new potential therapeutic uses. 1643 68