Growth hormone directly affects the function of the different lobes of the rat prostate.

Abstract

In this study, we investigated the involvement of GH in rat prostate function. First, we demonstrated that specific transcripts corresponding to the GH receptor (4.5 kilobases) and to the GH-binding protein (1.2 kilobases) were expressed in the normal rat prostate, but also in all prostatic carcinoma cell lines tested (LNCaP, PC-3, MAT-Lu, MAT-LyLu, and Pif-1). Moreover, these transcripts were much more abundant in the human and rat carcinoma cells than in the normal tissue. One-year-old dwarf rats were supplemented for 7 days with saline (group DR1) or highly purified rat GH (group DR2). Northern blotting and quantitation of prostatic messenger RNAs (mRNAs) revealed that GH increases the steady state levels of transcripts coding for androgen receptor (2.4-fold), type I and II 5 alpha-reductases (2.6- and 2.2-fold), and several androgen-dependent proteins [prostatein C3 subunit (3.6-fold), probasin (11.0-fold), and R. W. B. (Royal Winnipeg Ballet) (12.5-fold)]. This suggests that GH might either potentiate the action of androgens on the prostate or act directly on this gland by a mechanism that does not depend on testicular androgens. To address this question, we supplemented hypophysectomized and castrated adult rats for 7 days with saline (group HC1), rat GH (group HC2), testosterone propionate (group HC3), or GH plus testosterone (group HC4), starting 3 days after castration. In this animal model, the abundance of C3 mRNA increased in all hormone-treated rats; the stimulation factors were 3.5 (group HC2), 25.5 (group HC3), and 9.5 (group HC4) compared to group HC1. Analysis of prostatein synthesis by Western blotting confirmed these results at the protein level. The same trend was observed for probasin and RWB mRNA levels. Probasin mRNA increased 4.5-fold in group HC2 and 12-fold in group HC3, but did not increase in group HC4 (both hormones combined); enhancement of RWB mRNA was, respectively, 5.0-, 28.0-, and 15.0-fold in groups HC2, HC3, and HC4. GH did not affect the abundance of androgen receptor mRNA. As described previously, the level of this mRNA dropped significantly in group HC3. GH alone did not significantly alter the level of either 5 alpha-reductase mRNA, whereas testosterone, alone or with GH, produced a 2-fold increase in type II 5 alpha-reductase mRNA (groups HC3 and HC4). Type I isoenzyme mRNA reached 1.6 times the control level (group HC1) in groups HC3 and HC4.(ABSTRACT TRUNCATED AT 400 WORDS)

Obesity and metabolic dysfunction severely influence prostate cell function: role of insulin and IGF1

“…In this sense, as previous studies have indicated that the role of circulating GH in the PG is circumscribed to the stimulation of the local production of IGF1 , these data might also suggest the existence of an autocrine/paracrine GH/GHR loop potentially able to stimulate IGF1 production from the PG. Indeed, our results confirmed previous findings showing the expression of Igf1 , Igfr and Insr at the PG , and demonstrated the local expression of other components of the IGF1/insulin system such as various Igfbps ( Igfbp2 and Igfbp3 ) as well as of other associated proteins, as is the case of the glucose transporter Glut4 . Most importantly, as previously observed in other tissues , our results indicate that the expression pattern of the components of the GH, insulin and IGF1 regulatory axes can be finely modulated in the PG by environmental factors such as the diet.…”

“…Moreover, a growing body of evidence indicates that the endocrine axis comprising growth hormone (GH), insulin and insulin‐like growth factor 1 (IGF1) is locally expressed in the PG and plays a relevant role in its pathophysiology . Thus, earlier studies showed that pituitary‐produced GH is essential for PG development, controlling prostate size , and local expression of IGF1 and its receptor (IGF1R), in vivo and in vitro . IGF1 is a well‐known regulator of cell proliferation, differentiation and apoptosis , which is mainly produced by the liver , but is also expressed locally within the stromal and epithelial cells of PGs, where it can act as an autocrine/paracrine factor .…”

Disruption of Growth Hormone Signaling Retards Early Stages of Prostate Carcinogenesis in the C3(1)/T Antigen Mouse

“…Human prostate cancer cell lines such as LNCaP and PC3 express GH receptors (GHRs) at levels greater than observed in normal tissue (25). Pollak et al (26) reported that the growth of androgen-independent PC3 cells is slowed in GHdeficient Little mice (Ghrhr lit/lit ) relative to control mice.…”

Μεταβολές της ενδοθηλιακής συνθετάσης του μονοξειδίου του αζώτου (e-NOS) στον προστάτη αδένα των επιμύων μετά από αδρενεργικό αποκλεισμό

“…Μέχρι στιγμής δεν ήταν γνωστό το αν η ανάπτυξη του προστάτη αδένα απαιτούσε τις ίδιες ουσίες. Ο Reiter και συνεργάτες κατόρθωσαν να παράσχουν σημαντικά στοιχεία για το ότι η GH είναι δυνατόν να διαδραματίζει κάποιο ρόλο στην ανάπτυξη του προστάτη, καθώς διεγείρει την παραγωγή του mRNA, τόσο του IGF-Ι, όσο και του υποδοχέα του σε αυτόν 134,135 . Το γεγονός ότι η δομή του προστάτη αδένα σε ζώα στα οποία είχε αφαιρεθεί το γονίδιο του IGF-Ι δεν ανακτήθηκε μέσω της χορήγησης GH είναι συμβατό με την αντίληψη ότι η ανάπτυξη του προστάτη και του μαζικού αδένα είναι παρόμοιες όσον αφορά στον καταρράκτη που ακολουθεί την επαγόμενη από την GH παραγωγή του IGF-Ι.…”