Istituto Lombardo - Accademia di Scienze e Lettere - Incontri di Studio

SALUTO DEL PRESIDENTE DELL’ISTITUTO LOMBARDO

2020-04-05T21:34:19+00:00

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LUCIANO MARTINI: UNA PERSONALITÀ POLIEDRICA

2020-04-05T21:34:18+00:00

An internationally acclaimed authority in the field of Endocrinology and in particular of Neuroendocrinology, a brilliant and imaginative scientist, an intense and intellectual man, an illuminated and open mentor. These few words outline the profile of professor Luciano Martini. Luciano Martini created the first scientific group devoted only to experimental endocrinology which year after year grew up in number and visibility, became well recognised internationally and contributed to the development of new lines of research mainly in the field of neuroendocrinology, oncological endocrinology, physiology of reproduction, steroids and energetic metabolism.

LA DIFFERENZIAZIONE SESSUALE DEL CERVELLO NON È SOLO UNA QUESTIONE DI ORMONI

2020-04-05T21:34:17+00:00

One of the key events occurring during fetal brain development is the induction of permanent morpho-functional sexual differences in many brain areas. This “imprinting” mechanism, operating on a plastic brain within a narrow sensitive window, leads to gender-specific responses to the same stimulus both in neurochemistry/neuroendocrinology, and in some behavioral responses. The origin of CNS dimorphism is a topic that has fascinated neuroscientists for more than 60 years. The conventional view of brain sexual differentiation proposes that the masculine or feminine brain organization depends on the presence or absence of early gonadal steroid exposure: prenatal testosterone (T) surge in males induces both the masculinization and the defeminization of some brain nuclei, while in the absence of fetal gonadal hormones, as in females, the brain appears to feminize spontaneously. Some effects of T depend on its conversion to estradiol or DHT, two active metabolites formed by the enzymes aromatase and 5alpha-reductase type 2, respectively. Many studies carried out on rodents in our and in other laboratories clarified that estradiol and DHT are implicated in both masculinization and defeminization; on the contrary, T as such and DHT seem to be the main brain organizers in men. However, the most recent research, briefly discussed in this paper, has now clarified that the hormonal environment alone is not sufficient to trigger the whole process and that a precise coordination and interaction among hormonal signals, neuronal genome and the epigenome are pivotal to the genesis of brain gender-specific differentiation. Given the complexity of the whole process, it is not surprising that any external perturbation that brain sex differentiation may have heavy consequences on several parameters. Some possible variations related to prenatal exposure to environmental pollutants that interfere with the hormonal activity and/or the epigenome will be briefly analyzed in the final part of the paper.

ENZIMA 5ALFA-REDUTTASI NEL CERVELLO: UNA STORIA ANCORA COMPLICATA

2020-04-05T21:34:17+00:00

The enzyme 5alpha-reductase represents an important enzymatic pathway of the sex steroids, such as progesterone and testosterone. Its physiophatological role in the nervous system will be here discussed. Indeed, despite several observations have been obtained so far, several diagnostic and therapeutic aspects need to be clarified.

THE PHYSIOPATHOLOGICAL ROLES OF ANDROGENS IN MOTONEURONS

2020-04-05T21:34:16+00:00

The androgen receptor has been purified in the ‘70s and cloned in the ‘80s. It is a member of the steroid receptor superfamily and mediated the most important effects of androgen in androgen dependent or sensitive tissues. Several physiological function of the brain are differentially controlled in the two sexes and androgens play specific role in the processes of sexual differentiation and it is involved in the maintenance of male sex behaviour in adulthood. When mutated, the androgen receptor may impact on many of these androgen-regulated activities because of a loss of androgenic function in target cells. However, in the case of a peculiar type of mutation, the elongation of the polyglutamine tract normally present in its N-terminus, the androgen receptor becomes neurotoxic and induces cells death of a number of motoneurons in the spinal cord, which express very high level of this protein. Here, we will briefly discuss the most important actions of androgen receptor-mediated androgen activity in the brain and the mechanisms by which the mutant androgen receptor may lead to neurodegeneration in Spinal and Bulbar Muscular Atrophy (SBMA).

REGOLAZIONE DELLA FERTILITÀ: ARTE E NEUROSCIENZE

2020-04-05T21:34:15+00:00

The term ‘fertility’ (from Latin language getting abundant harvests) leads back to several fields of the sciences; however, when it is linked to the physiology of reproduction it became, along with nutrition, as a fundamental behavior for the living species. The ‘mystery’ of human reproduction has been an attractive issue and extensively represented in figurative arts (paintings, sculptures, ect.) throughout the centuries and different cultures, being itself an ‘art’. Many scientists have been so fascinated by the art to have modified their personal and scientific lives. Art and sciences, in particular the neurosciences, share their origin during human history, being both the expression of human abilities to formulate an abstract thought to understand and describe the complexity of the world around us. For instance, paintings as the Cabanel’s Birth of Venus as well as the Primavera by Botticelli summarize several aspects of the sexual desire and reproduction; however, the neurosciences provide a more complex and artistic picture of the control of fertility. From the first descriptions, by Geoffrey Harris and Luciano Martini, of the control of the hormonal cascade governing reproductive functions by the hypothalamus, an important region of our brain, it came to the identification of the GnRH, the master regulator of hormonal reproductive axis. GnRH is produced by specific hypothalamic neurons and it is released in the blood vessels directed toward the pituitary gland in a pulsatile manner, finely tuned for rhythm and intensity, to regulate the secretion of pituitary gonadotropins LH and FSH. Released gonadotropin will exert trophic and regulatory effects on gonadal functions and on the production of sex hormones (testosterone and estrogens). A number of neuroendocrine signals control the development and the activity of GnRH neurons and whose functional alterations are responsible of several reproductive system diseases. According to the data so far available, it is fair to say that the development of such complex mechanisms, under the brain control, endowed with the extraordinary ability to create new individuals could be a real artwork.

METABOLISMO ENERGETICO E RIPRODUZIONE: DUE FACCE DELLA STESSA MEDAGLIA

2020-04-05T21:34:14+00:00

Living organisms possess numerous physiological functions. Among these, some are absolutely common to all animal species and therefore also to human species. We refer to the control of the reproductive function and to that of the energetic metabolism, which, intuitively, are fundamental phenomena for the survival of the individual and of the species. Research conducted over many years in our laboratory, for a long time under the supervision of professor Luciano Martini, have helped to link these two basic functions for life, exploring the common molecular bases. In fact, it has been observed that many common molecular factors contribute to the regulation of both reproduction and energy metabolism, ie food intake and energy expenditure. A peculiar anatomical site where this interaction takes place is certainly the hypothalamus, a part of the brain that integrates a huge amount of impulses and that, moment by moment, regulates a variety of physiological functions, including these two. At this level, among the most interesting molecules there is neuropeptide Y, which is not only the most powerful stimulator of appetite, but also participates in the regulation of the first part of the reproductive axis: the gonadotropin-releasing hormone-gonadotropin system. Another important element of this network of regulatory molecules is kisspeptin, which, among others, is also crucial in starting the pubertal process, also in relation to nutritional status. The dialogue between peripheral organs, such as the tissue or rather the adipose “organ”, and central structures is also interesting. In fact, adipose produces hormones called adipokines, such as leptin, which, reaching the hypothalamus, promotes a sense of satiety by reducing the release of neuropeptide Y. Leptin itself, however, is also a fundamental permissive factor for the activation of the reproductive system. In short, fundamental functions such as the control of energy metabolism and reproduction are in fact regulated in part by the same molecules, which suggests a deep reciprocal relationship, which can be altered under various pathological conditions.

REPRODUCTIVE FUNCTION AND ANTITUMOR ACTIVITY: DIFFERENT ROLES FOR THE HYPOTHALAMIC HORMONE GnRH

2020-04-05T21:34:13+00:00

The decapeptide GnRH (Gonadotropin-Releasing Hormone), whose amino acidic sequence was discovered by Dr. A.V. Schally, was initially identified as the key hypothalamic hormone involved in the control of reproductive functions. GnRH, by binding to specific receptors (GnRH-R) at the pituitary level, stimulates the synthesis and secretion of the two gonadotropins (LH, luteinizing hormone and FSH, follicle stimulating hormone) and the downstream production of steroid hormones at the gonadal level. At present, these receptors represent the molecular targets of the standard pharmacological treatments for hormone-related tumors, such as androgen-dependent prostate cancer. Actually, chronic administration of synthetic GnRH agonists induces the desensitization of pituitary receptors and, subsequently, the suppression of testicular androgen production. The physiological role of GnRH in reproductive functions, and its regulation, represented a very important line of research for professor Martini and His colleagues. In the last three decades it has become increasingly clear that GnRH-R are expressed also in a wide range of tumors, both related and unrelated to the reproductive system; in particular GnRH-R are expressed in prostate cancers after development of resistance to androgen ablation therapy (castration resistant prostate cancer, CRPC), a tumor known to be refractory to standard chemotherapy. Activation of these receptors by means of GnRH agonists is associated with a significant antiproliferative/antimetastatic/antiangiogenic activity. These different biological effects at pituitary vs. prostate tissues are related to specific intracellular signal transduction pathways. Based on these observations, tumor GnRH-R are presently considered an effective molecular target for novel therapies (‘targeted’ therapies). In particular, GnRH-based bioconjugates, in which a standard cytotoxic drug is linked to a GnRH analog, have been developed. The rationale for this ‘targeted’ therapy is that the GnRH analog behaves as the targeting moiety by binding to GnRH-R in tumors, thus specifically delivering (targeting) the cytotoxic drug to tumor cells. At the level of tumor cells, the bioconjugate is internalized and degraded at the lysosomal level; in this way the anticancer drug is specifically released into the tumor cells to exert its cytotoxic effects, while sparing normal cells. In conclusion, GnRH-R are expressed not only at the pituitary level but also in a wide range of tumor tissues; these receptors are at present under investigation as an effective molecular target for the development of novel therapeutic strategies.

A WALK THROUGH LUCIANO’S ROLE IN INTERNATIONAL MEETINGS AND THE ROAD TO A NOVEL UNDERSTANDING OF SEX STEROID PHYSIOLOGY

2020-04-05T21:34:12+00:00

Luciano Martini has been an internationally renowned endocrinologist and a remarkable ambassador of Italian endocrinology through the world. He brought important experimental contributions in support of the new science of intracrinology. After the menopause, the secretion of estrogens stops while serum DHEA attains its lowest values. Estrogens and androgens are produced intra cellularly from the small residual amounts of DHEA. They act within the cells and are released only after inactivation, thus avoiding stimulation of the endometrium and possible actions in other tissues. In three independent 12-week prospective, randomized, double- blind and placebo-controlled clinical studies, it was shown that intravaginal administration of DHEA (prasterone) improves the severity score of the most bothersome symptom of the menopause such as vaginal dryness and dyspareunia. Most importantly, all serum sex steroids remained within normal values, thus explaining the absence of systemic effects. In conclusion, the lack of DHEA availability, not the lack of estrogens, is the main cause of the symptoms of menopause and this notion should guide the therapeutic strategy.

LO STORICO

2020-04-05T21:34:12+00:00

Professor Martini and I shared an interest in the history of the 20th century, with particular regard to the birth and development of Fascism and Nazism; we learned to swap books on this topic. When the occasion came up, we combined congress trips with visits to places that allowed us to deepen our historical knowledge.

LUCIANO MARTINI SCRITTORE

2020-04-05T21:34:11+00:00

Luciano Martini was an intelligent and accurate many-sided person who could have played, in his lifetime, many different professional roles and in fact left on this world clear footsteps of his versatility. In this short paper I am referring just to his literary activity. His main literary piece of work is an essay book dedicated to the figure of Geo Chavez, a young man who became interested to the first aircrafts that in fact had an extraordinary time of interest in France, at the beginning of the twentieth century. Chavez was due to be the first to succeed to cross the Alps by the aerial mean, although he unfortunately precipitated and lost his life at his arrival in Domodossola, on September 1910. I believe that the choice of Martini to tell this heroic and tragic story was due to a deep personal evaluation and to a strong affinity of civil and ethical values. Among the various subjects treated in this book, I wish to point out the cause of the fatal fall that took the life of the young Chavez. This cause was never fully understood since 1910, that is through a entire century but it is accurately discussed by Martini by means of a rational and passional approach worthy of a master who defends the memory of a young pupil lost while being in service. Martini resolutely refuses to believe that the fall of the aircraft might have been due to a human mistake in the maneuver of landing. He believes that the young Chavez was a pilot experienced enough to avoid such an elementary mistake. He is sure and does demonstrate that much more realistic is the hypothesis of a structural collapse of the aircraft itself. Therefore, Chavez fall was comparable to that of Icarus that accomplished his promised flight but finally precipitated due to the wax fusion of his wings. The fact that his fall happened just in the lowest ten meters of altitude was neither a reason of consolation nor of salvation.

IL DIDATTA

2020-04-05T21:34:10+00:00

Ars longa, vita brevis... Hippocrates of Kos, the medical doctor, taught us the importance of the study, which comes to terms with the transience of time. The life of prof. Luciano Martini was a perfect combination of study, science and art, values that over time he has instilled in many of us.

LUCIANO MARTINI: L’UOMO DELLE ISTITUZIONI

2020-04-05T21:34:09+00:00

I present Luciano Martini from some points of view that seem secondary but that have greatly influenced his scientific activity and his person: the comparison between the times in which Luciano began his scientific activity and the current situation in biomedical research, his encounter in Milan with professor Emilio Trabucchi, an enlightened and courageous Professor of pharmacology, his contribution to the development of experimental Endocrinology in Italy and worldwide and his ability to transport the scientific mentality to renew academic institutions. I close with a reminder of his work on Jeorge Chavez’s flight over the Alps and with a comment by Luigi Barzini “The car was destroyed and man was destroyed. But of the prodigious fact remains the memory that will never be destroyed” which is well suited to summarizing our emotion in remembering Luciano Martini today.

IL MUSICOLOGO

2020-04-05T21:34:08+00:00

Luciano Martini loved the music, of a love that entered directly into the category of passion. Thanks to the ability to read the music and a wide culture extended to other forms of art, he could get from the music maximum enjoyment. In the music field he had signed articles and held lectures. About his passion he was very reserved, opening himself to the discussion only with connoisseurs at his level. Likewise, the fact that he played the piano has remained completely private. Our relationship had found strong support in the mutual friendship and attendance of an opera singer that we had chosen as our favorite, Giuseppe Di Stefano. In recent years and until just before its end, musical topics and memories of moments lived with the great tenor have been the subject of long telephone conversations in which, together with the passion for music, his lucidity of judgment and his intelligence were readily apparent.

PROGRAMMA DEL CONCERTO CONCLUSIVO

2020-04-05T21:34:08+00:00

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TESTIMONIANZE

2020-04-05T21:34:07+00:00

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TESTIMONIANZE

2020-04-05T21:34:06+00:00

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TESTIMONIANZE

2020-04-05T21:34:05+00:00

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TESTIMONIANZE

2020-04-05T21:34:05+00:00

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