Pathology and genetics of tumours of the urinary system and male genital organs

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid peptide that was first isolated from ovine hypothalamic extracts on the basis of its ability to stimulate cAMP formation in anterior pituitary cells. PACAP belongs to the vasoactive intestinal polypeptide (VIP)-glucagon-growth hormone releasing factor-secretin superfamily. The sequence of PACAP has been remarkably well conserved during the evolution from protochordate to mammals, suggesting that PACAP is involved in the regulation of important biological functions. PACAP is widely distributed in the brain and peripheral organs, notably in the endocrine pancreas, gonads, and respiratory and urogenital tracts. Characterization of the PACAP precursor has revealed the existence of a PACAP-related peptide whose activity remains unknown. Two types of PACAP binding sites have been characterized. Type I binding sites exhibit a high affinity for PACAP and a much lower affinity for VIP whereas type II binding sites have similar affinity for PACAP and VIP. Molecular cloning of PACAP receptors has shown the existence of three distinct receptor subtypes, the PACAP-specific PAC1 receptor, which is coupled to several transduction systems, and the two PACAP/VIP-indifferent VPAC1 and VPAC2 receptors, which are primarily coupled to adenylyl cyclase. PAC1 receptors are particularly abundant in the brain and pituitary and adrenal glands whereas VPAC receptors are expressed mainly in the lung, liver, and testis. The wide distribution of PACAP and PACAP receptors has led to an explosion of studies aimed at determining the pharmacological effects and biological functions of the peptide. This report reviews the current knowledge concerning the multiple actions of PACAP in the central nervous system and in various peripheral organs including the endocrine glands, the airways, and the cardiovascular and immune systems, as well as the different effects of PACAP on a number of tumor cell types.

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: From Structure to Functions

Curcumin and cancer: An “old-age” disease with an “age-old” solution

Early detection of prostate cancer: AUA Guideline

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid C-terminally alpha-amidated peptide that was first isolated 20 years ago from an ovine hypothalamic extract on the basis of its ability to stimulate cAMP formation in anterior pituitary cells (Miyata et al., 1989. PACAP belongs to the vasoactive intestinal polypeptide (VIP)-secretin-growth hormone-releasing hormone-glucagon superfamily. The sequence of PACAP has been remarkably well conserved during evolution from protochordates to mammals, suggesting that PACAP is involved in the regulation of important biological functions. PACAP is widely distributed in the brain and peripheral organs, notably in the endocrine pancreas, gonads, respiratory and urogenital tracts. Characterization of the PACAP precursor has revealed the existence of a PACAP-related peptide, the activity of which remains unknown. Two types of PACAP binding sites have been characterized: type I binding sites exhibit a high affinity for PACAP and a much lower affinity for VIP, whereas type II binding sites have similar affinity for PACAP and VIP. Molecular cloning of PACAP receptors has shown the existence of three distinct receptor subtypes: the PACAP-specific PAC1-R, which is coupled to several transduction systems, and the PACAP/VIP-indifferent VPAC1-R and VPAC2-R, which are primarily coupled to adenylyl cyclase. PAC1-Rs are particularly abundant in the brain, the pituitary and the adrenal gland, whereas VPAC receptors are expressed mainly in lung, liver, and testis. The development of transgenic animal models and specific PACAP receptor ligands has strongly contributed to deciphering the various actions of PACAP. Consistent with the wide distribution of PACAP and its receptors, the peptide has now been shown to exert a large array of pharmacological effects and biological functions. The present report reviews the current knowledge concerning the pleiotropic actions of PACAP and discusses its possible use for future therapeutic applications.

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

Background

The prevalence of carcinoma of the prostate gland (CaP) and high-grade prostatic intraepithelial neoplasia (HGPIN) was assessed in a Spanish population, representative of the Caucasian Mediterranean (CM) ethnic group Data were compared with those described in populations from other geographical regions and in other ethnic groups



Methods

CaP and HGPIN were evaluated in a consecutive series of prostatic glands collected at the post-mortem examination of 162 male patients born and living in Spain, aged 20–80 years, and dying from trauma The glands were sliced every 2–3 mm All slices were paraffin embedded and sectioned to obtain 5 μm whole-mount sections To compare the prevalence rate in our series and in other Caucasian populations with that from other geographical areas and other ethnic groups, we used data from the autopsy study performed at the Wayne State University



Results

Prevalence of CaP is 358, 882, 1428, 2380, 317, and 3333% in the 3rd, 4th, 5th, 6th, 7th, and 8th decades, respectively The rates of HGPIN were 714, 1175, 3571, 3806, 4540, and 4815% at the 3rd, 4th, 5th, and 8th decades of life Both CaP and HGPIN are located preferentially at the peripheral zone of the gland and in 21/27 cases (777%), an association between CaP and HGPIN was found The prevalence of both lesions in CM males is significantly lower than in Caucasian American (CA) and Afro-American (AA) males in all the age groups evaluated



Conclusions

Microscopic foci of CaP and HGPIN can be documented in CM males from the 3rd decade of life onwards The lesions become more frequent and extensive as age increases The prevalence of both lesions seems to be significantly lower in the CM population than in CA and AA males in all the age groups evaluated Prostate 54: 238–247, 2003 © 2002 Wiley-Liss, Inc

Prevalence of prostate cancer and prostatic intraepithelial neoplasia in Caucasian Mediterranean males: an autopsy study.

Two different estrogen receptors (ER-alpha and ER-beta) have been described, which are differentially involved in regulating the normal function of reproductive tissues. ER-alpha was considered for a long time to be the only estrogen receptor, and it has been detected in the stromal cells of the human prostate but not in the epithelium. To obtain new information about the differential effects of both receptor types, we have investigated their localization in normal prostates, benign prostatic hyperplasia (BPH), and prostatic cancer (PC) by immunohistochemistry, ELISA and Western blot. Epithelial immunostaining was absent in normal prostates and was present in BPH (10% of cells) and PC (80% of cells), whereas about 15% of stromal cells were positively immunostained for ER-alpha in the three types of prostatic specimens studied. Epithelial immunostaining for ER-beta was detected in normal prostates (13% of cells), BPH (30% of cells) and PC (79% of cells), whereas stromal immunostaining for ER-beta was absent in normal and hyperplastic prostates and was present in PC (12% of cells). The complementary presence of both receptor types in the normal prostate (ER-beta in the epithelium and ER-alpha in the stroma) might explain the mechanism of estrogen action in the development of BPH. The increased epithelial immunostaining for both ER-alpha and ER-beta in BPH and PC suggests that the involvement of estrogen receptors in hyperplasia and cancer concerns mainly the epithelium.

/pdf/estrogen-receptors-alpha-and-beta-in-the-normal-hyperplastic-5f3u4l5qgs.pdf

Manuel Sánchez-Chapado

Papers

Prevalence of prostate cancer and prostatic intraepithelial neoplasia in Caucasian Mediterranean males: an autopsy study.

Estrogen receptors alpha and beta in the normal, hyperplastic and carcinomatous human prostate.

Renal Echinococcosis: Clinical Study of 34 Cases

Isolated retrovesical and extrarenal retroperitoneal hydatidosis: clinical study of 10 cases and literature review

Regulation of proliferation/apoptosis equilibrium by mitogen-activated protein kinases in normal, hyperplastic, and carcinomatous human prostate.