Steroidal ferrocenes as potential enzyme inhibitors of the estrogen biosynthesis.

The potential inhibitory effect of diverse triazolyl-ferrocene steroids on key enzymes of the estrogen biosynthesis was investigated. Test compounds were synthesized via copper-catalyzed cycloaddition of steroidal azides and ferrocenyl-alkynes using our efficient methodology published previously. Inhibition of human aromatase, steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) activities was investigated with in vitro radiosubstrate incubations.

Synthesis of methoxycarbonylpyrazolylandrostene derivatives, and their potential inhibitory effect on androgen biosynthesis and cell proliferation.

The Claisen condensations of 3β-acetoxypregn-5-en-20-one (1) and 3β-acetoxypregna-5,16-diene (7) with dimethyl oxalate are known to lead to 3β-hydroxy-21-methoxalylpregn-5-en-20-one (2) and 3β-hydroxy-21-methoxalylpregna-5,16-dien-20-one (8), respectively. The reactions of 2 with p-substituted phenylhydrazines afford pyrazol-5-yl derivatives (5) as main, and 3-yl regioisomers (4) as minor products. The corresponding reactions of 16-ene analogue 8 afford only pyrazol-5-yl regioisomer 9.

[In the labyrinth of calcium metabolism].

The authors present the case of a 27-year-old male patient. In 2010, he suffered from a bone fracture of the pelvis. As imaging techniques showed multiple osseal lytic lesions, diagnostic investigations were performed for multiple myeloma.

Novel series of 17β-pyrazolylandrosta-5,16-diene derivatives and their inhibitory effect on 17α-hydroxylase/C(17,20)-lyase.

The Claisen condensation of 3β-acetoxypregna-5,16-dien-20-one (1) with ethyl formate in the presence of sodium methylate in pyridine is known to lead to 3β-hydroxy-21-hydroxymethylidenepregna-5,16-dien-20-one (2) in good yield. With the methods described for the preparation of the saturated D-ring pyrazolyl series, the reactions of 2 with phenylhydrazine and its p-substituted derivatives in acetic acid resulted in mixtures of two steroidal regioisomers, the 1'-aryl-3'-pyrazolyl-(4a-e) and 1'-aryl-5'-pyrazolyl (5a-e) steroids. Compounds 4a-e are unknown in the literature.

Behavioral and endocrine effects of chronic exposure to low doses of chlorobenzenes in Wistar rats.

Chlorobenzenes have often been applied to study persistent organic pollutants with endocrine disruptor effects (POP/EDCs), but with the focus mainly on physiological aspects. Few data exist on the effects of chlorobenzenes and most POP/EDCs on anxiety or other arginine-vasopressin (AVP)- and oxytocin (OXT)-mediated behavior, albeit exposure to POP/EDCs or their ambient mixtures, even in low doses, may pose health risks for subjects living in contaminated areas and/or consuming polluted food. Our primary aim was therefore to demonstrate behavioral effects of longterm exposure to a discrete dose of a chlorobenzene mixture, and to draw attention to the results of subtoxic oral exposure on anxiety-related elements and the possible underlying endocrine processes.

[The importance of early diagnosis in acromegaly].

The authors review the historical and epidemiological aspects, clinical features and complications of acromegaly while emphasizing the importance of the early diagnosis and treatment. Acromegaly is a rare and mostly sporadic disorder due to excessive production of growth hormone. It is characterized by progressive somatic disfigurement (mainly involving the face and extremities) and systemic manifestations.

Further analysis of behavioral and endocrine consequences of chronic exposure of male Wistar rats to subtoxic doses of endocrine disruptor chlorobenzenes.

Many chemicals utilized by humans are present as environmental pollutants and may influence homeostasis from neurological, immunological, endocrinological and/or behavioral aspects. Such agents, acting alone or in ambient mixtures, may be biologically active even at extremely low doses, and it may be postulated that stable, bioaccumulative, reactive endocrine disruptors may affect central and/or peripheral secretion of arginine-vasopressin (AVP) and oxytocin (OXT) and thereby related physiological and behavioral functions, potentially leading to disorders in exposed subjects. The primary aim of this study was to demonstrate effects of chronic exposure to a low dose of an orally administered chlorobenzene mixture on anxiety-related and aggressive behavior mediated largely by AVP and OXT.

Determination of rat 5alpha-reductase type 1 isozyme activity and its inhibition by novel steroidal oxazolines.

The 5alpha-reductase type 1 isozyme is a key enzyme in the metabolism of the androgen steroid hormones and inhibitors of this enzyme represent a new pharmacological treatment for several androgen dependent diseases. We developed a radiosubstrate in vitro incubation method for the determination of 5alpha-reductase type 1 activity using rat liver microsomes as an enzyme source. With this method we have studied the inhibiting activity of novel (5' S)-17beta-(4,5-dihydrooxazol-5-yl)androst-5-en-3-one compounds containing various derivatized phenyl substituents coupled to the exo -heterocyclic moiety.

Steroselective synthesis of some steroidal oxazolines, as novel potential inhibitors of 17alpha-hydroxylase-C17,20-lyase.

17beta-Oxazolinyl steroids 7a-g and 8a-g were synthesized. The Lewis acid-catalysed reactions of (20R)-3beta-acetoxy-21-azidomethyl-20-hydroxypregn-5-ene with substituted aromatic aldehydes led to the formation of 3beta-acetoxyandrost-5-enes substituted in position 17beta with oxazolinyl residues (7a-g). Oppenauer oxidation of the 3beta-hydroxy-exo-heterocyclic steroids yielded the corresponding Delta(4)-3-ketosteroids.

Neighboring group participation Part 17 Stereoselective synthesis of some steroidal 2-oxazolidones, as novel potential inhibitors of 17alpha-hydroxylase-C(17,20)-lyase.

During the alkaline methanolysis of 3beta-acetoxy-21-chloropregn-5-ene-20beta-N-phenylurethane (4a), and its 4-monosubstituted (4b-e) and 3,5-disubstituted (4f) phenyl derivatives, cyclization occurs, in the course of which 17beta-[3-(N-phenyl)-2-oxazolidon-5-yl]androst-5-en-3beta-ol (5a) and its substituted phenyl derivatives (5b-f) are formed. The cyclization takes place with (N(-)-5) neighboring group participation. The reaction of 3beta-acetoxy-21-azidopregn-5-en-20beta-ol (3d) with triphenylphosphine gave 3beta-acetoxy-21-phosphiniminopregn-5-en-20beta-ol, which reacted in situ with carbon dioxide with the participation of the sterically favored 20beta-OH to give the unsubstituted steroidal cyclic carbamate (8).

Aortic stiffness is increased in acromegaly--a transthoracic echocardiographic study.

Background: Acromegaly is associated with increased cardiovascular risk. Recent studies suggested a direct effect of growth hormone and insuline-like growth factor 1 excess on the vasculature over the conventional risk factors. The aim of the present study was to evaluate the stiffness of ascending aorta by means of transthoracic echocardiography (TTE) in patients with acromegaly.

HPLC-RIA analysis of the ectopic cortisol production in a cancerous pancreas tumor.

Steroidal pathophysiology of a malignant, ACTH-producing pancreas tumor was investigated via HPLC-RIA determinations of intratissular concentrations of eleven main steroid hormones. The tumor specimen underwent extraction procedure with ethyl acetate and the extract was purified on a C18 minicolumn. Steroids were isolated by HPLC (C18-silica reversed phase stationary phase and methanol-water eluent system) and quantified by specific RIAs.

Stereoselective synthesis of some 17beta-dihydrooxazinyl steroids, as novel presumed inhibitors of 17alpha-hydroxylase-C17,20-lyase.

17beta-Dihydrooxazinyl steroids 5a-l and 6a-l were synthetized. The acid-catalyzed reactions of 21-azidomethyl-20-hydroxy- and 21-hydroxymethyl-20-azidosteroids with substituted aromatic aldehydes led to the formation of androst-5-en-3beta-ols substituted in position 17beta with dihydrooxazine residues. The inhibitory effects of these compounds on rat testicular C(17,20)-lyase were investigated with an in vitro radioincubation technique.

HPLC-RIA analysis of steroid hormone profile in a virilizing stromal tumor of the ovary.

The pathological steroid biosynthesis of a virilizing ovarian tumor was examined via high performance liquid chromatography-radioimmunoassay (HPLC-RIA) determination of the intratissular steroid concentrations. Sex cord-stromal tumor of the ovary was obtained surgically from an 18-year-old female patient with extremely high androst-4-ene-3,17-dione (4-en-dione) and testosterone (Test) blood serum levels. The tissue specimen was extracted with ethyl acetate and the extract was then purified on a C18 mini-column with methanol-water eluents.

Neighboring group participation. Part 15. Stereoselective synthesis of some steroidal tetrahydrooxazin-2-ones, as novel presumed inhibitors of human 5alpha-reductase.

During the alkaline methanolysis of 3beta-acetoxy-21-chloromethyl-pregn-5-ene-20beta-N-phenylurethane, and its p-substituted phenyl derivatives, cyclization occurs, in the course of which 17beta-[3-(N-phenyl)tetrahydrooxazin-2-on-6-yl]androst-5-en-3beta-ol and its p-substituted phenyl derivatives are formed. The cyclization takes place with (N(-)-6) neighboring group participation. Oppenauer oxidation of the 3beta-hydroxy-exo-heterocyclic steroids yielded the corresponding delta4-3-ketosteroids.

[Octreotide therapy in multiple endocrine neoplasia type-1].

In multiplex endocrine neoplasia type 1, hyperparathyroidism, pancreas tumor and pituitary tumor are generally combined. The authors report two patients with this syndrome, in whom overproduction of parathormone and gastrin was detected, and parathyroid adenomas were detected by parathyroid scintigraphy. Pancreatic adenomas were discovered with somatostatin receptor scintigraphy or magnetic resonance imaging.

[Current alternative in the pharmacotherapy of acromegaly: the long-acting somatostatin analogue octreotide].

Twelve active acromegalic patients (10 women, 2 men) were chronically treated with a long-acting microcapsulated preparation of octreotide (Sandostatin LAR, Novartis). In each case, a growth hormone-producing pituitary adenoma was responsible for the development of acromegaly (microadenomas in 3 and macroadenomas in the rest of the patients). Treatment with long-acting octreotide was indicated for those patients who had not reacted satisfactorily upon previous therapeutic procedures or proved to be unsuitable for irradiation therapy and/or surgery or refused both of these therapies.

[Suckling-induced changes in oxytocin and alpha-melanocyte-stimulating hormone contents of the median eminence and various lobes of the pituitary gland].

Previous reports have implicated that pituitary-derived prolactin (PRL) is secreted from two distinct zones of mammotropes within the anterior lobe (AL). The inner zone (AL-IZ), located adjacent to the NIL, is supposed to be involved in the rapid and massive discharge of PRL from the pituitary gland due to suckling stimulus. Anatomically, the AL-IZ has an intimate contact with the NIL because the blood arriving from the posterior pituitary through the short portal vessels (SPV) baths it first.

Asphyxia-induced release of alpha-melanocyte-stimulating hormone in newborn pigs.

Asphyxia and reperfusion induced changes in the plasma and cerebrospinal fluid (CSF) concentrations of alpha-melanocyte-stimulating hormone (alpha-MSH) were studied in newborn pigs using a specific radioimmunoassay technique. Cardiovascular and metabolic failure induced by neonatal asphyxia resulted in a 3-fold, significant (P < 0.05) increase in plasma alpha-MSH levels, whereas the hormone concentration in CSF was significantly (P < 0.

Functional membrane changes due to tumor induction in rat pituitary cell cultures.

Membrane functions in tumorous cells are different from those in healthy cells. The aim of the present study was to investigate the changes in pituitary cell membrane functions and hormone secretion after tumor induction in vivo and in vitro. Prolactinomas were induced in vivo in female Wistar rats with estrone acetate.

Involvement of endogenous corticotropin-releasing factor in mediation of neuroendocrine and behavioral effects to alpha-melanocyte-stimulating hormone.

The present work was to study if the alpha-melanocyte-stimulating hormone (alpha-MSH) was involved in activation of the pituitary-adrenal axis (PAA) in rats. The hormone increased plasma corticosterone (CORT) level, and induced an anxiogenic response as indicated by results from the elevated plus-maze test. Intracerebroventricular administration of corticotropin-releasing factor (CRF) antiserum (1:10, 1:20 and 1:100 dilutions in 1microl volume), overcame both the anxiogenic response and the PAA activating effect induced by alpha-MSH (50 microg s.

Suckling-induced change in oxytocin but not in alpha-MSH concentrations of the median eminence, the neural-, intermediate- and anterior lobes of the pituitary gland.

Previous reports have implicated that pituitary-derived prolactin (PRL) is secreted from two distinct zones of mammotropes within the anterior lobe (AL). The inner zone (AL-IZ), located adjacent to the neuro-intermediate lobe (NIL), is supposed to be involved in the rapid and massive discharge of PRL from the pituitary gland due to suckling stimulus. Whereas the outer-zone (AL-OZ) gives the basal secretion and it does not play a role in the acute secretory response during nursing.

[Minimally invasive adrenalectomy with posterior retroperitoneoscopy].

Authors report a total of 14 adrenalectomies performed from a posterior (lumbotomy) approach, using minimally invasive retroperitoneoscopic technique. The "UltraCision" scalpel, an ultrasound activated cutter-coagulation device has been used for operative tissue dissection. Two cases were converted.

Surface changes and hormone production in pituitary cells during tumorigenesis.

Prolactinomas were induced by chronic estrone acetate treatment in female Wistar rats in vivo. After enzymatic dissociation of the tumor tissue, monolayer cell cultures were obtained. In vitro tumor induction was performed by treatment of normal monolayer anterior pituitary cell cultures with a 1:1 mixture of 7,9-dimethylbenz[c]acridine: 8-methylbenz[c]acridine.