The partial purification and characterization of GnRH-like activity from prostatic biopsy specimens and prostatic cancer cell lines

Qayum, A; Gullick, William J.; Mellon, K.; Krausz, Thomas; Neal, David E.; Sikora, Karol; Waxman, Jonathan

doi:10.1016/0960-0760(90)90440-v

Cited by 29 publications

(9 citation statements)

References 8 publications

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“…Recently, the existence of a functional LHRH system in the prostate has been postulated [1]. This system comprises locally produced LHRH-like peptides and LHRH receptors [1,[35][36][37][38]. Its significance for the regulation of prostatic growth is still poorly understood.…”

Section: Discussionmentioning

confidence: 98%

Synergistic activation of androgen receptor by androgen and luteinizing hormone-releasing hormone in prostatic carcinoma cells

et al. 1997

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Section: Discussionmentioning

confidence: 98%

Synergistic activation of androgen receptor by androgen and luteinizing hormone-releasing hormone in prostatic carcinoma cells

et al. 1997

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“…LHRH immunoreactivity has been detected in breast [53], in prostate [54] and in ovarian [55] cancer cells. These preliminary observations have been later confirmed by several reports demonstrating that the mRNA coding for the LHRH peptide is expressed in hormone-related cancers [35,43,45,47,48,[55][56][57].…”

Section: Lhrh In Cancer Tissuesmentioning

confidence: 98%

LHRH analogues as anticancer agents: pituitary and extrapituitary sites of action

Limonta¹,

Marelli²,

Moretti³

2001

Expert Opinion on Investigational Drugs

102

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Two classes of luteinising hormone-releasing hormone (LHRH) analogues have been developed so far to be used for oncological therapies: LHRH agonists and antagonists. LHRH agonists are widely and successfully used for the management of steroid-dependent malignancies. Chronic administrations of these compounds result in downregulation and desensitisation of pituitary LHRH receptors and, therefore, in a complete suppression of gonadal function. LHRH agonist administration is effective, safe and reversible, suffering only from the 'flare-up' phenomenon at the beginning of treatment. LHRH antagonists suppress the pituitary-gonadal function by competing with native LHRH for binding to its pituitary receptor but without giving rise to the intracellular cascade of events evoked by the natural hormone or LHRH agonists. Synthetic peptides belonging to the last generations of LHRH antagonists have already been successful in clinical trials. They are completely devoid of the 'flare-up' phenomenon and seem to be free of side effects, such as histamine release. Recently, the expression of LHRH and LHRH receptors has been reported in a number of hormone-responsive tumours. In contrast with the pituitary LHRH receptor which is coupled to the Gq/11-PLC intracellular system of events, stimulation of the tumour LHRH receptor by LHRH is followed by the activation of a Gi protein and a decrease in cAMP levels. This intracellular pathway mediates the inhibitory action of the autocrine/paracrine LHRH system on tumour cell proliferation. The activation of LHRH receptors at tumour level may then represent an additional and more direct mechanism of action for the antitumoural activity of LHRH agonists. Surprisingly, LHRH antagonists also exert a marked antimitogenic activity on a number of hormone-responsive cancer cell lines, indicating that these compounds might behave as antagonists at pituitary level and as agonists at the level of the tumour. The observation that the inhibitory LHRH autocrine system is also present in some steroid-unresponsive cancer cell lines might suggest a possible clinical utility of LHRH analogues also for those tumours that have escaped the initial phase of hormone dependency.

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“…Although Miles et al (2004) demonstrated pro-apoptotic effects of GnRH in LβT2 gonadotrope cells, the effect was very small (only 10% of the cells), required prolonged incubation time with GnRH and may represent a non-physiological effect. It is thought that sex hormone sensitive cancer cells secrete GnRH and that GnRH interacts with the cells in an autocrine and sustained manner (Qayum et al, 1990a,b). On the other hand, hypothalamic GnRH acts on pituitary gonadotropes in a pulsatile manner.…”

Section: Discussionmentioning

confidence: 99%

“…However, several reports have demonstrated evidence of a direct effect of GnRH upon sex hormone-dependent tumors including prostate cancer cells (Bahk et al, 1998; Dondi et al, 1994, 1998; Emons et al, 1996, 1997, 1998; Jungwirth et al, 1997; Kraus et al, 2004, 2006; Limonta et al, 1992, 1993, 1999; Moretti et al, 1996; Qayum et al, 1990a,b; Wells et al, 2002). Binding sites, expression of GnRH and its receptor (GnRHR) and direct growth regulatory effects of GnRH in the above cancer cells have been reported (Bahk et al, 1998; Dondi et al, 1994, 1998; Emons et al, 1996, 1997, 1998; Jungwirth et al, 1997; Kraus et al, 2004, 2006; Limonta et al, 1992, 1993, 1999; Moretti et al, 1996; Qayum et al, 1990a,b; Wells et al, 2002). Regarding signaling of GnRHR in cancer cells, GnRH was reported either not to affect (Emons et al, 1996), or to stimulate phosphoinositide (PI) turnover (Imai et al, 1993; Keri et al, 1991; Segal-Abramson et al, 1992; Wells et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Differential signaling of the GnRH receptor in pituitary gonadotrope cell lines and prostate cancer cell lines

Sviridonov

Dobkin-Bekman

Shterntal

et al. 2013

Molecular and Cellular Endocrinology

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The GnRH receptor (GnRHR) mediates the pituitary functions of GnRH, as well as its anti-proliferative effects in sex hormone-dependent cancer cells. Here we compare the signaling of GnRHR in pituitary gonadotrope cell lines vs. prostate cancer cell lines. We first noticed that the expression level of PKCα, PKCβII and PKCε is much higher in αT3-1 and LβT2 gonadotrope cell lines vs. LNCaP and DU-145 cell lines, while the opposite is seen for PKCδ. Activation of PKCα, PKCβII and PKCε by GnRH is relatively transient in αT3-1 and LβT2 gonadotrope cell lines and more prolonged in LNCaP and DU-145 cell lines. On the otherhand, the activation and re-distribution of the above PKCs by PMA was similar for both gonadotrope cell lines and prostate cancer cell lines. Activation of ERK1/2 by GnRH and PMA was robust in the gonadotrope cell lines, with a smaller effect observed in the prostate cancer cell lines. The Ca2+ ionophore A23187 stimulated ERK1/2 in gonadotrope cell lines but not in prostate cancer cell lines. GnRH, PMA and A23187 stimulated JNK activity in gonadotrope cell lines, with a more sustained effect in prostate cancer cell lines. Sustained activation of p38 was observed for PMA and A23187 in Du-145 cells, while p38 activation by GnRH, PMA and A23187 in LβT2 cells was transient. Thus, differential expression and re-distribution of PKCs by GnRH and the transient vs. the more sustained nature of the activation of the PKC-MAPK cascade by GnRH in gonadotrope cell lines vs. prostate cancer cell lines respectively, may provide the mechanistic basis for the cell context-dependent differential biological responses observed in GnRH interaction with pituitary gonadotropes vs. prostate cancer cells.

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The partial purification and characterization of GnRH-like activity from prostatic biopsy specimens and prostatic cancer cell lines

Cited by 29 publications

References 8 publications

Synergistic activation of androgen receptor by androgen and luteinizing hormone-releasing hormone in prostatic carcinoma cells

Synergistic activation of androgen receptor by androgen and luteinizing hormone-releasing hormone in prostatic carcinoma cells

LHRH analogues as anticancer agents: pituitary and extrapituitary sites of action

Differential signaling of the GnRH receptor in pituitary gonadotrope cell lines and prostate cancer cell lines

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