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M. Motta and L. Martini

Abstract.

The intraventricular injection of 25 μg of Methionine-Enkephalin (Met-Enk) induces a significant increase of serum LH levels in long-term ovariectomized rats 15, 30 and 60 min following administration. The synthetic Met-Enk agonistic analogue [D-Ala2]Methionine-Enkephalinamide ([D-Ala2]Met-Enk) also enhances significantly serum LH levels at 30 and 60 min; under the same experimental conditions neither Met-Enk nor [D-Ala2]Met-Enk modifies serum levels of FSH following intraventricular injections into ovariectomized animals. It is concluded that, under particular circumstances, opioid peptides of the Met-Enk family may stimulate LH release.

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L. Martini, G. Giuliani and M. Motta

ABSTRACT

A new method of testing steroid-induced corticotrophin (ACTH) suppression is described. This is based on the observation that in the rat one single injection of corticotrophin-inhibiting steroids is capable of reducing plasma corticosterone levels 4 hours after treatment.

Details are given for obtaining both a rough estimation of the »absolute« ACTH-suppressive potency of a steroid and the more accurate »relative« estimation of potency; for comparative estimations it is proposed to use dexamethasone (9α-fluoro-16α-methyl-prednisolone) as reference standard.

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M. Legori, M. Motta, M. Zanisi and L. Martini

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E. Messi, M. Zanisi, F. Celotti and M. Motta

Abstract. The aim of the present study was to test the hypothesis that the restoring effect of testosterone on hypothalamic GnRH stores in orchidectomzied rats might be linked to the intrahypothalamic transformation of the hormone into estrogenic metabolites. To this purpose, advantage has been taken of the availability of the potent antiestrogen, tamoxifen (TMX). Different groups of adult male rats castrated since 4 weeks were submitted to a 6-day treatment with testosterone propionate (TP, 2 mg/rat daily); TMX (50 or 200 μg/rat daily); or TP (2 mg/rat daily) plus TMX (50 or 200 μg/rat daily). The animals were sacrificed 24 h after the last injection, and hypothalamic GnRH content was measured by radioimmunoassay. The results have confirmed the ability of TP to counteract the decreasing effect of orchidectomy on hypothalamic GnRH stores, and have shown that TMX does not have any intrinsic activity on this parameter. Furthermore, TMX at either dose used in the present experiments, was found not to be able to abolish the restoring effect of TP on MBH-GnRH stores. It is concluded that the action of testosterone on hypothalamic GnRH does not require the conversion of the hormone into estrogens.

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M. Motta, G. Lugaro, F. Piva and L. Martini

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P. Negri-Cesi, F. Celotti, R. C. Melcangi, M. Zanisi and M. Motta

Abstract. The aim of the present experiments was to analyze whether the inhibitory effect exerted by testosterone on FSH release might be mediated by the intracerebral transformation of the hormone into oestrogenic metabolites. Advantage has been taken of the availability of the potent antioestrogen tamoxifen. Two series of experiments have been performed. In the first one, adult male rats have been castrated and submitted, beginning immediately after surgery, to a 6-day treatment with testosterone propionate (2 mg/rat/day), tamoxifen (50 or 200 μg/rat/day) or testosterone propionate (2 mg/rat/day) plus tamoxifen (either 50 or 200 μg/rat/day). In the second experiment, adult male rats have been castrated and submitted to the same 6-day treatments, beginning 4 weeks following orchidectomy. In both experiments, the animals were killed 24 h after the last injection, and serum levels of FSH and LH have been measured by radioimmunoassays. The results have clearly shown that, in both experiments, the administration of testosterone results in a significant decrease of serum FSH and in a total suppression of LH release. The administration of tamoxifen, in either dose, does not modify the elevated serum FSH and LH levels present in the orchidetomized animals, and does not antagonize the inhibitory effect on FSH and LH secretion exerted by the concomitant treatment with testosterone propionate. It is concluded that testosterone inhibits FSH secretion in orchidectomized rats acting as such, and not following aromatization to oestrogens.

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H. Steiner, M. Motta, F. Piva, D. Gillessen and R. O. Studer

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Teresa M Seccia, Diego Miotto, Michele Battistel, Raffaella Motta, Marlena Barisa, Carmela Maniero, Achille C Pessina and Gian Paolo Rossi

Background

A stress reaction involving increased cortisol release, which has not been documented thus far, might affect the assessment of selectivity of catheterization during adrenal venous sampling (AVS).

Objective

To investigate whether an ACTH-driven cortisol release occurs during AVS and whether it influences the assessment of selectivity by the step-up of cortisol (plasma cortisol concentrations, PCC) between the adrenal vein blood (PCCSIDE) and the inferior vena cava (PCCIVC), e.g. the selectivity index (SI).

Design and methods

We determined the SI in samples obtained simultaneously at starting AVS (t-15) and again after 15 min (t0) in 34 consecutive patients with proven aldosterone-producing adenoma. We then calculated the SI with PCCSIDE obtained at t-15 and at t0, and the PCCIVC values obtained at the different time point, thus simulating sequential AVS.

Results

The PCCSIDE and the SI fell significantly from t-15 to t0 on both the sides. When PCCSIDE obtained at t-15 was combined with PCCIVC at t0, the SI values were higher than those obtained with simultaneously drawn samples. This led to label as selective more AVS studies than with bilaterally simultaneous data, especially when using higher cutoffs for the SI.

Conclusions

A transient increase in cortisol release from both adrenal glands occurs in the majority of the patients who undergo AVS. This stress reaction can influence the assessment of both the selectivity of the catheterization during the sequential AVS technique and the lateralization of aldosterone excess.

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Marco Bonomi, Valeria Vezzoli, Csilla Krausz, Fabiana Guizzardi, Silvia Vezzani, Manuela Simoni, Ivan Bassi, Paolo Duminuco, Natascia Di Iorgi, Claudia Giavoli, Alessandro Pizzocaro, Gianni Russo, Mirella Moro, Letizia Fatti, Alberto Ferlin, Laura Mazzanti, Maria Chiara Zatelli, Salvo Cannavò, Andrea M Isidori, Angela Ida Pincelli, Flavia Prodam, Antonio Mancini, Paolo Limone, Maria Laura Tanda, Rossella Gaudino, Mariacarolina Salerno, Pregnolato Francesca, Mohamad Maghnie, Mario Maggi, Luca Persani and Italian Network on Central Hypogonadism

Objective

Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and non-reproductive anomalies might be present although information on their frequency are scanty, particularly according to the age of presentation.

Design

Observational cohort study carried out between January 2008 and June 2016 within a national network of academic or general hospitals.

Methods

We performed a detailed phenotyping of 503 IHH patients with: (1) manifestations of hypogonadism with low sex steroid hormone and low/normal gonadotropins; (2) absence of expansive hypothalamic/pituitary lesions or multiple pituitary hormone defects. Cohort was divided on IHH onset (PPO, pre-pubertal onset or AO, adult onset) and olfactory function: PPO-nIHH (n = 275), KS (n = 184), AO-nIHH (n = 36) and AO-doIHH (AO-IHH with defective olfaction, n = 8).

Results

90% of patients were classified as PPO and 10% as AO. Typical midline and olfactory defects, bimanual synkinesis and familiarity for pubertal delay were also found among the AO-IHH. Mean age at diagnosis was significantly earlier and more frequently associated with congenital hypogonadism stigmata in patients with Kallmann’s syndrome (KS). Synkinesis, renal and male genital tract anomalies were enriched in KS. Overweight/obesity are significantly associated with AO-IHH rather than PPO-IHH.

Conclusions

Patients with KS are more prone to develop a severe and complex phenotype than nIHH. The presence of typical extra-gonadal defects and familiarity for PPO-IHH among the AO-IHH patients indicates a common predisposition with variable clinical expression. Overall, these findings improve the understanding of IHH and may have a positive impact on the management of patients and their families.