Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum levels of LH, FSH and testosterone (T) were measured by radioimmunoassays in 36 patients with advanced prostate cancer before and during androgen ablation therapies. Both leuprolide acetate (LH-RH agonist: LHRH-A) and diethylstilbestrol diphosphate (DES-DP) administration decreased serum LH significantly to an undetectable level (LHRH-A: P < 0.01, DES-DP: P < 0.05). LHRH-A and DES-DP diminished serum FSH to 20% of the pre-treatment level (P < 0.005) and to an undetectable level (P < 0.001), respectively. LHRH-A and DES-DP decreased serum T to the castration level and an undetectable level, respectively (P < 0.001). Serum levels of the same 3 hormones before and after DES-DP administration were measured in 8 patients who received DES-DP after LHRH-A treatment or castration because of relapse of the disease. DES-DP lowered serum FSH further than LHRH-A to an undetectable level (P < 0.005) and diminished T further than previous treatments to an undetectable level (P < 0.05 vs. LHRH-A, P < 0.01 vs. castration). These results suggest that 1) DES-DP is able to reduce T production from extra-testicular site(s), and achieve the minimal serum T level, and 2) this DES-DP action appears to be one of the mechanisms of the effectiveness of the estrogen on refractory prostate cancer after castration or LHRH-A. In addition, basal (independent of LH-RH) FSH secretion in elderly men is about 20% of total FSH secretion and DES-DP inhibits the basal FSH secretion at the level of the pituitary.
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PMID:Stronger suppression of serum testosterone and FSH levels by a synthetic estrogen than by castration or an LH-RH agonist. 944 85

The objective of this study was to elucidate the mechanism underlying the further suppression of serum testosterone (T) by diethylstilbestrol diphosphate (DES-DP) in patients with prostate cancer refractory to hormonal treatment. These patients received an LHRH agonist with or without a non-steroidal androgen-receptor blocker or a gestagen before DES-DP. We measured serum levels of total and free T, dihydrotestosterone (DHT), estradiol (E2), dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), androstenedione, cortisol, aldosterone before and during intravenous administration of high doses of DES-DP (500 or 1000 mg/day). DES-DP administration suppressed the serum levels of FSH (p=0.04) and total T (p=0.02), and eliminated free T (p=0.04) and E2 (p=0.04) from serum, while reducing serum DHEA-S to approximately two-thirds of the pretreatment level (p=0.03). In contrast, serum levels of SHBG (p=0.02) and cortisol (p=0.02) were markedly increased after DES-DP administration. The latter had no significant effect on serum levels of LH, DHT, ACTH, 17alpha-hydroxypregnenolone, 17alpha-hydroxyprogesterone, DHEA, androstenedione, or aldosterone. The results suggest that the potent suppression of circulating total T by DES-DP is caused, in part, by the inhibitory effect of DES-DP on serum DHEA-S level. In most patients, high-dose DES-DP treatment completely suppressed the serum level of free T, while possibly elevating serum SHBG and decreasing serum total T. The mechanisms that maintain the serum level of serum DHT during DES-DP treatment require further elucidation.
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PMID:Effects of intravenous administration of high dose-diethylstilbestrol diphosphate on serum hormonal levels in patients with hormone-refractory prostate cancer. 1067 Jul 51

Analogues of luteinizing hormone-releasing hormone (LH-RH) have made possible new approaches to the treatment of some hormone-dependent cancers and diseases and conditions which result from inappropriate sex hormone levels. In the fields of both gynaecology and oncology, the development of sustained delivery depot systems has played a key role in the clinical use of LH-RH agonists and will be also essential for the LH-RH antagonists. Clinical results show that therapy with agonists of LH-RH is the preferred method of treatment for men with advanced prostate cancer. For prostate cancer and other indications, the new LH-RH antagonists such as Cetrorelix may offer an advantage based on the fact that they inhibit LH, FSH and sex-steroid secretion from the start of the administration and thus reduce the time of the onset of therapeutic effects. The use of antagonists would avoid the temporary clinical "flare-up" of the disease which can occur with the agonists in men with prostate cancer. The rapid shrinkage of the prostate and improvement in urinary symptoms obtained with Cetrorelix in men with benign prostatic hyperplasia (BHP) suggests that LH-RH antagonists offer a therapeutic alternative in patients who are considered poor surgical risks. Various experimental and clinical studies suggest that analogues of LH-RH might be useful for treatment of premenopausal women with oestrogen-dependent breast cancer. LH-RH antagonists such as Cetrorelix could be also considered for hormonal therapy of epithelial ovarian cancer which responds only marginally to the agonists, and for treatment of endometrial cancer. Many investigators have reported beneficial effects of LH-RH agonists in the treatment of patients with leiomyomas. LH-RH antagonists also appear to be promising for therapy of uterine leiomyomas, and in addition might be useful for treatment of endometriosis and polycystic ovarian disease (PCOD). LH-RH agonists have been employed in in vitro fertilization and embryo transfer (IVF-ET) programs to prevent a premature rise in LH and various results suggest that the use of antagonist Cetrorelix in assisted reproduction procedures, could be even more advantageous. For most of these indications, the use of sustained release depot preparations will be required.
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PMID:Rational use of agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH) in the treatment of hormone-sensitive neoplasms and gynaecologic conditions. 1083 70

Successful prostate cancer diagnosis and management continue to provide challenges for the clinician. While interventions aimed at the containment of both early and late disease continue to fail in a significant number of patients, the search for answers must incorporate an analysis of the processes of normal and aberrant growth and development within the gland itself. Inhibin and its structurally related protein, activin, are members of the transforming-growth-factor beta (TGFbeta) superfamily. Originally identified as regulators of FSH, these proteins are now recognised to have widespread biological functions. This might be expected of proteins that are structurally homologous to TGFbeta itself, which is recognised to have regulatory roles in both normal and malignant prostate tissue. The aim of this review is to examine the relationship between inhibins, activins and their related proteins and the development of prostate cancer. The homology with TGF, the pluripotent effects of activin on various tissues and the roles for inhibins in ovarian cancer make activins and inhibins candidate growth factors for involvement at multiple sites in the progression from benign disease to cancer. In compiling this review, we aim to delineate the changes in inhibins and activins in this pathway and in doing so implicate their potential roles in the progression of carcinogenesis. We will compare the changes in inhibin and its related proteins in prostate cancer to those that are known in ovarian cancer. We will discuss the similarities and differences between the putative role of activins and TGFbeta in prostate carcinogenesis. The importance of this review lies in demonstrating that inhibin, an endocrine hormone, and its related proteins may contribute to endocrine-related cancers, such as that of the prostate gland.
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PMID:The role of inhibins and activins in prostate cancer pathogenesis. 1117 46

The pineal hormone melatonin is the mediator of external light to physiologic adaptation to day and night rhythms, it regulates reproduction in animals but attempts to utilize melatonin in women for contraception have failed. Melatonin seems to be the natural hormone to facilitate sleep in insomniac patients and causes no hang over. When applied together with benzodiazepine it allows reduction of benzodiazepine without withdrawal effects. It should be applied 2 h before sleeping time in doses between 3 and 5 mg. Melatonin acts via the gamma-aminobutyric acid- and benzodiazepine receptor explaining its success in treatment of seizures in children and in adults. Constant application of benzodiazepine reduced the production of natural melatonin in rats, supporting the evidence that long-term application of benzodiazepine in humans does not restore sleeping habits but reduces natural sleeping habits even more. Low melatonin levels were seen in bulimia or neuralgia and in women with fibromyalgia; replacement reduced pain, sleeping disorders, and depression in fibromyalgia and bulimia. Melatonin profiles are a diagnostic tool to distinguish between several forms of depression, like major depression, winter depression (SAD), unipolar depression, delayed sleep phase syndrome (DSPS). In patients with a major depression success with antidepressants correlated with an increase in their melatonin profiles but only patients suffering from DSPS can be successfully treated with melatonin. In perimenopausal women melatonin administration did produce a change in LH, FSH and thyroid hormones. Some oncostatic properties are supported by cell culture work and studies in animals. In Nordic countries indigenous people suffer less from breast and prostate cancer, winter darkness seems to protect. The supposedly increased melatonin levels created the 'melatonin hypothesis'. Epidemiological studies did show that blind people indeed have half the rate of breast cancers, supporting the hypothesis. Controversial results concerning melatonin and insulin resistance and glucose tolerance have been published. In postmenopausal women application of melatonin reduced glucose tolerance and insulin sensitivity. Pregnant women should avoid melatonin, since its teratogenic effect is not known. Patients suffering from non-hormone dependent tumors, like leukemia, should avoid melanin, since tumor growth was promoted in animal experiments. It can be expected that melatonin will receive wide consideration for treatment of sleeping disturbances, jet lag, and fibromyalgia once an oral formulation becomes available in Europe.
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PMID:Melatonin deficiencies in women. 1195 97

Gonadotropin-releasing-hormone (GnRH) analogues are synthetic compounds derived from decapeptide neurohormones (LHRH; LH/FSH-RH). They have a key role in hormone dependent cancer, particularly breast and prostate cancer. GnRH analogues produce an efficient inhibition of gonadotropins and sex steroid hormones. Their use in cancer therapy result in a, pharmacological castration (i.e. ovariectomy and orchiectomy), providing an androgen and estrogen ablation. GnRH exert an inhibitory action on the growth of hormone-dependent human and canine mammary tumor. Mammary tumors can produce growth factor that potentially could modulate their own proliferation in an autocrine fashion (i.e. TGF-alpha and TGF-beta or with a paracrine mechanism (i.e. EGF, IGF, FGF). The expression of EGF receptors is related in mammary tissues to the action of oestrogen and progesteron and to the presence of functional receptors for oestrogen (ER) and progesteron (PR). The present review elucidate the role of GnRH receptors in cancer and their connection with steroid hormones. Besides we showed the link between GnRH and signal transductions pathways: Estrogen-receptors, GnRH-receptors, EGF-receptors signal transduction pathways. A very tight link exists between steroid hormones and GnRH analogues both on central pituitary gonadal axis and on tumor receptors peripherically. This last mechanism could be explained either locally activating GnRH receptors or locally interacting with EGF receptor-Intracellular NitricOxide system.
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PMID:GnRH and steroids in cancer. 1204 4

Aims of this study: From cross-sectional and longitudinal population based studies as well as from autopsy studies it is well documented that total prostate volume increases with advancing age. However, it is not well known (1) which factors are ultimately responsible for this growth phenomenon; or (2) at what time in a persons life the growth tends to occur. At present at least a permissive role for testicular androgens is assumed to be involved in growth regulation. Other factors such as growth factors, epithelial-mesenchymal interaction, and the role of intact neural pathways are still poorly understood. We aimed to study a group of men with spinal cord injuries to determine whether the pattern of prostate enlargement would be different in men with partially or completely interrupted innervation of the pelvis and the prostate gland. Materials and methods: Forty-three men from the Spinal Cord Injury (SCI) Service at the VA North Texas Health Care System ranging in age from 27-73 y (mean 51 y) were recruited to participate in this study. Time since SCI ranged from 2-47 (mean 19 y). All patients underwent standardized questionnaire, physical examination, transrectal ultrasonography (TRUS) measurements of total and transition zone volume of the prostate, serum PSA, testosterone (T), dihydrotestosterone (DHT), FSH and LH measurements, some had TRUS guided biopsies taken. Results: By all the measured criteria there were no abnormalities regarding the pituitary-gonadal axis observed in these men. Testicular volume, serum T, DHT and LH were within normal ranges, and when the patients were stratified by age, no differences were identified. There was an age related increase in FSH which has been described in neurologically intact men. Serum PSA increased slightly with advancing age. While total (TPV) and transition zone (TZV) prostate volume increased with age, the groupwise differences by decades of life were not significant. Moreover, when compared to a group of community dwelling men without known prostatic diseases and a clinic cohort of men with BPH, TPV was substantially lower for each decade of life except for men in their 40s, while TZV was substantially lower for men in their 60s. Conclusions: We observed normal age related changes regarding serum PSA and serum FSH without significant changes in other hormonal parameters. All parameters behaved consistent with changes described in neurologically intact populations. However, we did not observe the typical increase in TPV and TZV of the prostate as seen in population, autopsy and clinic patient studies. This interesting finding indicates that factors other than an intact pituitary-gonadal axis and male steroid hormones may be responsible for the normal age related growth of the prostate. Further studies in larger cohorts are needed to corroborate our findings.
Prostate Cancer Prostatic Dis 1998 Sep
PMID:Characterization of prostate size, PSA and endocrine profiles in patients with spinal cord injuries. 1249 84

We report here two cases of pituitary apoplexy or pseudoapoplexy revealing a gonadotroph adenoma. A 69-year-old man, who had just started antiandrogen treatment (Gn-RH agonist) for prostatic cancer, was admitted to neurosurgery emergency because of increasing headache and visual impairment. The CT-scan disclosed the presence of a large pituitary mass with lateral invasion of the left cavernous sinus. Hormonel testing showed panhypopituitarism. A few days later, diabetes insipidus appeared. The patient first received corticosteroid therapy and underwent surgical adenomectomy. Immunostaining of the tumor tissue was positive for FSHbeta, confirming the diagnosis of gonadotroph adenoma. Three months after surgery, the endocrine evaluation showed pituitary insufficiency. An 81-year-old man complained of mnemonic disorders. The CT-scan revealed a pituitary mass without extension. The Ophthalmological examination showed left temporal upper quadranopsia. Endocrinological tests with administration of GN-HR triggered headache and vomiting. A second CT-scan was unchanged. Hormone testing revealed increased serum levels of FSH and decreased serum levels of LH. Surgical management of the primary tumor was undertaken due to the visual field alteration. Immunohistochemical studies confirmed the diagnosis of gonadotroph FSHbeta adenoma.
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PMID:[Two cases of non-functional gonadotroph adenoma pituitary apoplexy following GnRH-agonist treatment revealing gonadotroph adenoma and pseudopituitary apoplexy after GnRH administration]. 1291 66

Activins are multifunctional growth and differentiation factors and stimulate FSH-beta gene expression and FSH secretion by the pituitary gonadotropes. Follistatins bind activin, resulting in the neutralization of activin bioactivity. The activin/follistatin system is present in the prostate tissue. Prostate-specific antigen (PSA) plays an important role in male reproductive physiology as well as being very important as a tumor marker for prostate cancer. Thus the regulation of PSA has important clinical implications. Previous studies showed that PSA is primarily regulated by androgens. In the present study, we evaluated the direct effects of activin A on the proliferation and PSA production of prostate cancer LNCaP cells, which express functional activin receptors and androgen receptor and PSA. LNCaP cells were treated with activin A and 5alpha-dihydrotestosterone (DHT) with or without their antagonists (follistatin or the nonsteroidal anti-androgen bicalutamide). Activin A decreased cell growth of LNCaP cells in a dose-dependent manner, whereas DHT increased it in a biphasic manner. In contrast to their opposing actions on cell growth, both activin A and DHT upregulated PSA gene expression and increased PSA secretion by LNCaP cells. The effects of activin A and DHT to increase PSA production were synergistic or additive. Follistatin or bicalutamide was without effect on cell growth or PSA production. The effects of activin A on LNCaP cells were blocked by follistatin, not by bicalutamide, whereas effects of DHT were prevented by bicalutamide, not by follistatin. Activin A upregulates PSA production, and the effect is through an androgen receptor-independent pathway. The activin/follistatin system can be a physiological modulator of PSA gene transcription and secretion in the prostate tissue, and activins may cooperate with androgen to upregulate PSA in vivo.
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PMID:Regulation of prostate-specific antigen by activin A in prostate cancer LNCaP cells. 1476 77

Inhibin was first identified as a gonad-derived regulator of pituitary FSH; however, it has subsequently been shown to be a tumour suppressor in the gonad and adrenal glands. Whereas non-malignant regions of human primary prostate carcinomas express inhibin alpha-subunit (INHA), malignant tissues lack INHA transcript and protein, which is consistent with epigenetic regulation of the inhibin alpha-subunit gene (INHA) promoter. This study investigated whether methylation of the INHA promoter was responsible for inactivation of INHA transcription and translation in the prostate cancer cell lines, LNCaP, DU145 and PC3. Methylation of the promoter was revealed by bisulphite genomic sequencing and use of inhibitors of methylation and histone deacetylation resulted in reactivation of the INHA transcription and translation. Significant (P<0.05) downregulation of a luciferase reporter gene downstream from a methylated INHA promoter compared with unmethylated INHA promoter occurred in vitro. The data demonstrate that promoter methylation is associated with downregulation of the INHA gene in prostate cancer cell lines, which is consistent with its tumour suppressive role. Therefore INHA has a significant role in prostate tumorigenesis.
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PMID:Epigenetic regulation of inhibin alpha-subunit gene in prostate cancer cell lines. 1476 92


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