1,720,971 research outputs found
Ruolo dei recettori dell'LH e del GnRH nell'iperaldosteronismo primitivo: studi clinici e molecolari
Full text linkPrimary aldosteronism (PA) is characterized by a chronic, excessive and autonomous adrenal aldosterone secretion. The mechanism causing steroids production in adrenal adenoma and hyperplasia remains poorly defined. Within the adrenal gland, ectopic expression of G-protein-coupled receptors (GPCRs) has been shown to cause excessive production of cortisol in some cases of ACTH-independent Cushing's syndrome. Recently, it has been demonstrated that some GPCRs (serotonin 5-HT4 receptor, V1-vasopressin receptor, GIP receptor, LH/hCG and GnRH receptors) are abnormally expressed in aldosteronomas.
The aim of our study was to investigate the role of LH-GnRH receptors as potential regulators of aldosterone secretion. We first investigated a patient (index case) with new diagnosis of PA during pregnancy and then extended our study to a wider group of patients to evaluate through, in vivo and molecular analysis, the possible clinical fallout of the data previously reported.
A GnRH stimulation test was performed in 12 patients affected by PA and in 5 controls. In the index case we also measured aldosterone levels after chorionic gonadotropin and a long-acting GnRH analogue. RTPCR was performed to evaluate GnRH and LH receptors in 23 PA and 6 normal tissues. Immunohistochemistry was done in 16 and 7 samples for LH and GnRH receptors respectively.In vivo GnRH test showed a variable increase of aldosterone levels in 10 patients with a positive response (>50%) in 3 of them (in 2 higher than 100%). An increase of plasma aldosterone was also observed after chorionic gonadotropin injection and Triptorelin administration in the index case. Aldosterone levels were not modified by GnRH infusion in control subjects. RT-PCR showed the presence of LH receptor in 22 out of 23 PAs and in normal tissues with comparable levels. GnRH receptor was detected at low levels in normal tissues whereas 7 PA tissues presented an expression significantly higher than normal adrenal glands. Two single APA samples exhibited the highest GnRH receptor expression (95-fold and 109-fold). Immunostaining identified the presence of the LHR protein in 12/16 PA and GnRHR protein in 7/7 APA tissues. In the index case GnRH staining was positive mainly in the aldosteronoma and lesser in the adjacent adrenal.
In conclusion, we observed that in a high percentage of patients with PA, plasma aldosterone seems to respond variably to GnRH stimulation; in a subset of patients, aldosterone response is significantly elevated. Molecular and immunohistochemical studies for LH receptor showed a similar expression in normal and tumoral tissues. The expression of GnRH receptor was significantly elevated in a subgroup of patients with PA compared to normal adrenal glands. In the index case, clinical and molecular data suggest that during pregnancy the patient may have been exposed to high levels of placental GnRH that can potentially activate the overexpressed adrenal GnRH receptor. These results support the concept of LH or GnRH dependent aldosterone secretion in a subset of patients with APA and IHA. The use of GnRH test in patients with a suggestive medical history (pregnancy, menopause, primary hypogonadism) can provide useful data to clarify PA pathogenesis and for the clinical follow-up.L'iperaldosteronismo primitivo (PA) è caratterizzato da una cronica, eccessiva e autonoma secrezione di aldosterone da parte delle ghiandole surrenaliche. I meccanismi che guidano la sintesi degli steroidi negli adenomi e nelle iperplasie surrenaliche rimangono da chiarire. Recenti studi hanno dimostrato che in alcuni casi di sindrome di Cushing ACTH indipendente la secrezione di cortisolo può essere regolata dalla presenza di recettori ormonali illeciti legati alle proteine G (GPCR) espressi nel tessuto surrenalico. Recenti dtudi molecolari suggeriscono che alcuni GPCR (il recettore serotoninergico 5-HT4, il recettore per la vasopressina V1, il recettore per il GIP, e i recettori per LH/hCG e per GnRH) possono essere espressi in maniera aberrante anche in tumori surrenalici secernenti aldosterone.
Lo scopo del nostro lavoro è stato quello di approfondire il ruolo dei recettori dell'LH e del GnRH come potenziali regolatori dell'iperincrezione di aldosterone. Il lavoro si è svolto partendo dallo studio clinico di una paziente affetta da PA insorto in gravidanza (caso indice) e successivamente esteso ad una casistica più ampia di pazienti per indagare attraverso test in vivo e studi molecolari la possibile ricaduta clinica dei dati molecolari finora riportati in letteratura.
Per effettuare questo lavoro abbiamo valutato la risposta in vivo dell'aldosterone al GnRH in 12 pazienti affetti da PA e in 5 soggetti sani; nel caso indice abbiamo valutato la risposta dell'aldosterone plasmatico anche dopo gonadotropina corionica e un analogo long-acting del GnRH. Abbiamo studiato l'espressione tissutale attraverso Real Time PCR dei recettori dell'LH/hCG e del GnRH in 23 tessuti patologici e in 6 surreni sani; l'indagine immunoistochimica per i due recettori è stata condotta rispettivamente in 16 adenomi per il recettore LH/hCG e in 7 per il recettore del GnRH. Il Test al GnRH ha documentato un incremento variabile dei livelli di aldosterone in 10 sui 12 pazienti studiati con una risposta positiva (>50%) in 3 casi in due dei quali l'incremento è stato superiore al 100%. Il caso indice ha evidenziato una risposta positiva dell'aldosterone anche dopo gonadotropina corionica mentre dopo triptorelina si è osservata un progressivo aumento dei livelli plasmatici di aldosterone. In nessuno dei soggetti di controllo vi è stato un incremento dei livelli di aldosterone dopo stimolo. Lo studio del recettore per LH attraverso RTPCR ha evidenziato la presenza del recettore nei surreni normali e in 22 su 23 campioni patologici con dei livelli di espressione comparabili tra i due gruppi. Il recettore per il GnRH è risultato essere presente nei surreni normali anche se con un valore medio di espressione molto basso mentre in 7 tessuti patologici l'espressione del gene è risultata significativamente elevata (in due casi di 95 e 109 volte rispetto al tessuto surrenalico normale).
L'analisi immunoistochimica ha identificato il recettore dell'LH in 12 su 16 casi di aldosteronoma e il recettore del GnRH in tutti e 7 i campioni studiati. La paziente del caso indice presentava una intensa positività per il recettore del GnRH del tessuto adenomatoso e meno nel tessuto peritumorale circostante. In conclusione, nella nostra casistica, in un'elevata percentuale di pazienti con PA l'aldosterone plasmatico sembra rispondere, seppur in modo variabile, allo stimolo con GnRH; in un sottogruppo di pazienti la percentuale di risposta dell'ormone è significativamente elevata. Gli studi molecolari e di immunoistochimica condotti per il recettore dell'LH hanno evidenziato che si tratta di un recettore che oltre che presentare un'espressione eutopica è presente anche nella maggior parte dei tessuti patologici con dei livelli di espressione simili. L'espressione del recettore del GnRH è risultata significativamente elevata in un sottogruppo di pazienti affetti da PA rispetto ai surreni normali. I dati molecolari e di immunoistochimica e i risultati dei test condotti in vivo nel pre e nel post operatorio del caso indice suggeriscono che durante la gravidanza la paziente possa essere stata esposta ad elevati livelli di GnRH di origine placentare in grado potenzialmente di attivare i recettori surrenalici del GnRHR iperespressi. I risultati del nostro lavoro supportano l'ipotesi che in un sottogruppo di pazienti affetti da PA la secrezione di aldosterone possa essere LH o GnRH dipendente. L'utilizzo del test al GnRH in pazienti con una storia clinica suggestiva (gravidanza, menopausa, ipogonadismo primitivo) potrebbe fornire dati utili per chiarire la patogenesi dell'iperaldosteronismo e per il successivo follow-up clinico
Idiopathic primary hyperaldosteronism: normalization of plasma aldosterone after one month withdrawal of long-term therapy with aldosterone-receptor antagonist potassium canrenoate
No full textWe have re-evaluated 15 patients with idiopathic primary aldosteronism one month after withdrawal of therapy with aldosterone-receptor antagonist potassium canrenoate. Therapy had lasted for 3 to 24 yr. Median blood pressure (BP) in the sitting position at the time of diagnosis was 160/100 (ranges 150-200/95-110 mmHg); while 1 month after withdrawal of therapy median BP was 145/90 (ranges 125-160/80-100 mmHg). One month after withdrawal, the ratio aldosterone (ng/dl)/plasma renin activity (ng/ml/h) in the upright position was increased only in 3 cases (median 18, range 6.1-125). We found a significant inverse correlation between the upright aldosterone/plasma renin activity (aldo/PRA) ratio, 1 month after withdrawal, and the number of years of therapy with potassium canrenoate. We conclude that long-term therapy with the aldosterone-receptor blocker, potassium canrenoate, can normalize the aldo/PRA ratio in many cases of idiopathic primary hyperaldosteronism after one-month withdrawal of the drug. These data are consistent with possible regression of idiopathic primary hyperaldosteronism after long-term therapy with potassium canrenoate, or in alternative to a persistent effect of potassium canrenoate, on aldosterone synthesis
Spironolactone in the treatment of polycystic ovary syndrome: effects on clinical features, insulin sensitivity and lipid profile
No full textThis prospective clinical trial was designed to assess the effects of a long-term therapy with spironolactone, with and without dietary-induced weight-loss, on clinical features, lipid profile and insulin levels in women with polycystic ovary syndrome (PCOS). Twenty-five patients (range of age 16-32 yr; 13 lean and 12 overweight) fulfilling formal diagnostic criteria for PCOS (oligomenorrhea and/or amenorrhea, biochemical and/or clinical evidence of hyperadrogenism) were studied at baseline and then received oral spironolactone (100 mg/die) for 12 months; association with lifestyle modifications was recommended to all over-weight patients. Clinical, endocrine and metabolic parameters [oral glucose tolerance test (OGTT), lipid profile] were measured at baseline and at the end of the antiandrogen treatment. The therapy was associated with a significant average decline of triglycerides in overweight subjects and with increased HDL-cholesterol levels in lean patients. The insulin levels at 60 min during OGTT, homeostasis model assessment-insulin resistance and area under curve of insulin were significantly lowered in overweight women after 12 months of spironolactone and weight loss and no negative changes in insulin secretion and sensitivity were observed in PCOS women after pharmacological treatment alone. The efficacy of spironolactone on the androgenic clinical aspects of PCOS has been confirmed in this study. Furthermore, our data show that long-term treatment with spironolactone exerts no negative effects on lipoprotein profile and glucose metabolism; more relevant beneficial effects on glucose and lipid metabolism were observed when the antiandrogen was associated with weight loss in overweight PCOS women
Effect of licorice on PTH levels in healthy women
No full textLicorice has been considered a medicinal plant for thousands of years. Its most common
side effect is hypokalemic hypertension, which is secondary to a block of 11-hydroxysteroid
dehydrogenase type 2 at the level of the kidney, leading to an enhanced mineralocorticoid
effect of cortisol. This effect is due to glycyrrhetinic acid, which is the main constituent of
the root, but other components are also present, including isoflavans, which have estrogenlike
activity, and are thus involved in the modulation of bone metabolism. We investigated
nine healthy women 22–26 years old, in the luteal phase of the cycle. They were given
3.5 g of a commercial preparation of licorice (containing 7.6%, w/w of glycyrrhizic acid)
daily for 2 months. Plasma renin activity (PRA), aldosterone, cortisol, serum parathyroid
hormone (PTH), 1,25-dihydroxy Vitamin D (1,25OHD), 25-hydroxycholecalciferol (25OHD),
estradiol, FHS, LH, alkaline phosphatase (ALP), calcium, phosphate and creatinine, urinary
calcium and phosphate and mineralometry were measured. PTH, 25OHD and urinary calcium
increased significantly frombaseline values after 2months of therapy, while 1,25OHD
and ALP did not change during treatment. All these parameters returned to pretreatment
levels 1month after discontinuation of licorice. PRA and aldosterone were depressed during
therapy, while blood pressure and plasma cortisol remained unchanged. Conclusions: licorice
can increase serum PTH and urinary calcium levels from baseline value in healthy women
after only 2 months of treatment. The effect of licorice on calcium metabolism is probably
influenced by several components of the root, which show aldosterone-like, estrogen-like
and antiandrogen activity
Licorice reduces serum testosterone in healthy women
No full textLicorice has been considered a medicinal plant for thousands of years. The most common side effect is hypokalemic hypertension, which
is secondary to a block of 11-hydroxysteroid dehydrogenase type 2 at the level of the kidney, leading to an enhanced mineralocorticoid
effect of cortisol. We have investigated the effect of licorice on androgen metabolism in nine healthy women 22–26 years old, in the luteal
phase of the cycle. They were given 3.5 g of a commercial preparation of licorice (containing 7.6% W.W. of glycyrrhizic acid) daily for two
cycles. They were not on any other treatment. Plasma renin activity, serum adrenal and gonadal androgens, aldosterone, and cortisol were
measured by radioimmunoassay. Total serum testosterone decreased from 27.8±8.2 to 19.0±9.4 in the first month and to 17.5±6.4 ng/dL
in the second month of therapy (p < 0.05). It returned to pre-treatment levels after discontinuation. Androstenedione, 17OH-progesterone, and
LH levels did not change significantly during treatment. Plasma renin activity and aldosterone were depressed during therapy, while blood
pressure and cortisol remained unchanged.
Conclusions: licorice can reduce serum testosterone probably due to the block of 17-hydroxysteroid dehydrogenase and 17–20 lyase. Licorice
could be considered an adjuvant therapy of hirsutism and polycystic ovary syndrome
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
- …
