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Biomedical subjects

R Maggi

Publications and source records attributed to R Maggi.

At least 55 records · Page 3Linked to original sources
PubMed1993

Androgen and progesterone metabolism in the central and peripheral nervous system.

This paper summarizes the most recent data obtained in the authors' laboratory on the metabolism of testosterone and progesterone in neurons, in the glia, and in neuroblastoma cells. The activities of the 5 alpha-reductase (the enzyme that converts testosterone into dihydrotestosterone, DHT), and of the 3 alpha-hydroxysteroid dehydrogenase (the enzyme that converts DHT into 5 alpha-androstane-3 alpha, 17 beta-diol, 3 alpha-diol) have been first evaluated in primary cultures of neurons, oligodendrocytes and type-1 and -2 astrocytes, obtained from the fetal or neonatal rat brain. All the cultures were used on the fifth day. The formation of DHT of 3 alpha-diol was evaluated incubating the different cultures with labeled testosterone or DHT as substrates. The results obtained indicate that the formation of DHT takes place preferentially in neurons; however, type-2 astrocytes and oligodendrocytes also possess considerable 5 alpha-reductase activity, while type-1 astrocytes show a much lower enzymatic concentration. A completely different localization was observed for 3 alpha-hydroxysteroid dehydrogenase; the formation of 3 alpha-diol appears to be prevalently, if not exclusively, present in type-1 astrocytes; 3 alpha-diol is formed in very low yields by neurons, type-2 astrocytes and oligodendrocytes. The compartmentalization of two strictly correlated enzymes (5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase) in separate central nervous system (CNS) cell populations suggests the simultaneous participation of neurons and glial cells in the 5 alpha-reductive metabolism of testosterone. Subsequently it has been shown that, similarly to what happens when testosterone is used as the substrate, the 5 alpha-reductase which metabolizes progesterone into 5 alpha-pregnane-3,20-dione (DHP) shows a significantly higher activity in neurons than in glial cells; however, type-1 and -2 astrocytes as well as oligodendrocytes also possess some ability to 5 alpha-reduce progesterone. On the other hand, 3 alpha-hydroxysteroid dehydrogenase, the enzyme which converts DHP into 5 alpha-pregnane-3 alpha-ol-20-one, appears to be present mainly in type-1 astrocytes; much lower levels of this enzyme are present in neurons and in type-2 astrocytes. At variance with the previous results obtained using androgens as precursors, oligodendrocytes show considerable 3 alpha-hydroxysteroid dehydrogenase activity, even if this is statistically lower than that present in type-1 astrocytes. The existence of isoforms of the enzyme involved in androgen and progesterone metabolism is discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1993

Testosterone and progesterone metabolism in the human neuroblastoma cell line SH-SY5Y.

The ability of the human neuroblastoma cell line SH-SY5Y to metabolize androgens and progesterone was studied by incubating the cells in the presence of labeled testosterone (T) or progesterone (P) to measure, respectively, the formation of dihydrotestosterone (DHT) or dihydroprogesterone (DHP) (5 alpha-reductase activity). The 3 alpha-hydroxysteroid dehydrogenase activity was studied by evaluating the conversion of labeled DHT into 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol). The results show that undifferentiated neuroblastoma cells possess a significant 5 alpha-reductase activity, as shown by the considerable conversion of T into DHT; moreover, this enzymatic activity seems to be significantly stimulated following cell differentiation induced by the phorbol ester TPA, but not after differentiation induced by retinoic acid (RA). The 5 alpha-reductase(s) present in SH-SY5Y cells is also able to convert P into DHP. In undifferentiated cells, this conversion was about 8 times higher than that of T into DHT. Under the influences of TPA and RA, the formation of DHP followed the same pattern observed for the formation of DHT. SH-SY5Y cells also appear to possess the enzyme 3 alpha-hydroxysteroid dehydrogenase, since they are able to convert DHT into 3 alpha-diol. This enzymatic activity is not altered following TPA-induced differentiation and appears to be decreased following treatment with RA. It is suggested that the SH-SY5Y cell line may represent a useful "in vitro" model for the study of the mechanisms involved in the control of androgen and P metabolism in nervous cells.

20-alpha-Dihydroprogesterone↗
PubMed1993

Binding characteristics of hypothalamic mu opioid receptors throughout the estrous cycle in the rat.

This study presents a detailed analysis of the binding characteristics of hypothalamic mu opioid receptors during the different phases of the estrous cycle of the female rat. Different groups of adult female rats with a regular 4-day estrous cycle were killed by decapitation at 10.00 h of diestrus days 1 and 2, at 10.00, 12.00, 14.00, 16.00, 18.00 and 20.00 h of the day of proestrus and at 10.00, 12.00, 14.00, 16.00 and 18.00 h of the day of estrus. At sacrifice, the hypothalami of the animals were dissected out, plasma membrane preparations were obtained and the binding characteristics (Bmax, Kd) of the specific mu opioid ligand dihydromorphine (DHM) on mu opioid receptors were evaluated. Blood has been collected from the trunk vessels to monitor with specific radioimmunoassays serum levels of LH, estradiol and progesterone. The data obtained indicate that in the hypothalamus of female rats with a regular 4-day estrous cycle, the binding characteristics of DHM for mu receptors show important variations during the different phases of the estrous cycle. In general, the number of mu opioid receptors is elevated during the morning of diestrus day 2 and during the day of proestrus being maximal at 14.00 h and declining significantly at 18.00 and 20.00 h of the same day. At estrus, the number of mu receptors appears high at 10.00 and 16.00 h and low at 12.00, 14.00 and 18.00 h. All these variations take place without any significant change of the affinity (Kd) of DHM for the mu receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Repeated gestational trophoblastic disease after natural and heterologous assisted conception. A case report.

We report the case of a woman with a familial history of gestational trophoblastic disease who developed repeated partial and complete moles after fertilization by her husband and heterologous assisted conception. This case has interesting etiologic implications, but it is difficult to make any extrapolation from this very peculiar case in terms of definition/quantification of maternal and paternal components in the development of gestational trophoblastic disease.

Adult↗
PubMed1993

Ageing of the neuroendocrine system in the brain of male rats: receptor mechanisms and steroid metabolism.

The work described in this article gives information on the effects of ageing on the hypothalamo-pituitary-testicular axis in rats. The hypothalami of young and old male rats contain similar amounts of luteinizing-hormone-releasing hormone (LHRH); when perifused in vitro they release comparable amounts of LHRH under basal conditions and in response to K+. The addition of an LHRH analogue to the perifusion medium blocks the release of LHRH induced by K+ from the hypothalami of young and old male rats, indicating that the ultrashort feedback mechanism controlling LHRH release functions normally in aged male rats. Ageing also exerts important effects on the density of mu- and kappa-opioid receptors in the brain. The number of hypothalamic mu-opioid receptors was significantly decreased in aged animals; a replacement treatment with testosterone does not reverse this decrease, indicating that the decline of hypothalamic mu receptors and of serum titres of testosterone in old rats are independent phenomena. The number of kappa-opioid receptors in the brain increases in the amygdala and in the thalamus with ageing. Apparently ageing does not influence the number of delta receptors in any of the brain areas investigated. The number of pituitary LHRH receptors decreases in old animals, which might explain the low serum concentration of gonadotrophins in aged rats caused by an inadequate response of the pituitary to hypothalamic LHRH. The impaired secretion of testosterone in aged male rats is accompanied by an increase in the number of testicular LHRH receptors, indicating that the intratesticular mechanisms controlling testosterone release also undergo significant alterations during ageing. The rate of conversion of testosterone to dihydrotestosterone (DHT) and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) is the same in the hypothalami of young and old rats. However, the yields of DHT obtained from the pituitaries of aged male rats are significantly lower than those recorded in the pituitaries of young animals. These results show that the enzymes necessary for metabolizing testosterone via the 5 alpha-reductase pathway are maintained both in the hypothalamus and in the anterior pituitary of aged male rats. However, the 5 alpha-reductase activity of the anterior pituitary of senescent animals appears to be lower than that in the younger controls.

Aging↗
PubMed1993

Gonadotropin releasing hormone agonist for chronic anovulatory uterine bleeding and severe anemia.

Twenty-three women with chronic heavy anovulatory uterine bleeding and severe iron-deficiency anemia received six months' treatment with goserelin, a gonadotropin releasing hormone agonist, administered as a monthly subcutaneous depot. After two months of treatment, all patients were amenorrheic and subsequent spotting was reported on only nine occasions. Laboratory results showed the following values: mean hemoglobin before treatment, 7.9 g/dL-13.8 g/dL at six months (+75%); mean hematocrit, 26.3%-41.6% (+58); mean serum iron, 19.8 micrograms/dL-63.3 micrograms/dL (+134%) and mean serum ferritin, 6.2 ng/mL-35.3 ng/mL (+469%). The endometrial hyperplasia observed in 11 subjects showed regression at follow-up suction biopsy. Gonadotropin releasing hormone agonists administered in a depot formulation for a few months in highly selected patients with severe anemia associated with heavy anovulatory uterine bleeding are practical, safe and effective, may avoid blood transfusions and could be used as a first line of treatment.

Adult↗
PubMed1993

Endocervical detection of CIN. Cytobrush versus cotton.

Correct methods of sampling are essential for obtaining adequate smears for cytological diagnosis of cervicovaginal abnormalities. In this paper we report on 3 methods of sampling, Ayre spatula, cotton swab and cytobrush on 89 patients who underwent repeat smear and colposcopic examinations because of abnormal screening smears. The cytobrush device was better than Ayre spatula or cotton in collecting both endocervical and neoplastic cells. However, the combination of spatula and cotton was almost the same as spatula and cytobrush in recovering neoplastic cells. Therefore the rate of cervical intraepithelial neoplasia (CIN) diagnosis is more influenced by an adequate sampling of the endocervix than by the type of endocervical device.

Adult↗
PubMed1992

Gonadotropin releasing hormone agonist treatment for severe menorrhagia in patients with contraindications to surgery.

Four patients with heavy menorrhagia, severe iron-deficiency anemia and contraindications to surgery were treated with a gonadotropin-releasing hormone agonist in a depot formulation. At 2 months of therapy they were all amenorrheic, and at 6 months the hematologic values had improved markedly. Gonadotropin-releasing hormone agonists may obviate emergency surgery in patients at high surgical risk or could constitute the first line of sequential therapeutic regimens, once general health conditions have improved.

Adult↗
PubMed1992

Binding characteristics of delta opioid receptors in different regions of the brain of young and old male rats as studied with the highly selective ligand [D-Pen2-D-Pen5] enkephalin.

The present experiments were performed to study the binding characteristics of delta opioid receptors in membrane preparations obtained from the brain of adult male rats, and to analyze whether aging modifies these binding parameters. The binding characteristics of delta opioid receptors were evaluated on membrane preparations derived from dissected brain regions (hypothalamus, amygdala, mesencephalon, corpus striatum, hippocampus, thalamus, frontal poles, anterior and posterior cortex) collected from male rats of 3 and 24 months of age; the highly selective ligand 3H-[D-Pen2-D-Pen5] enkephalin (3H-DPDPE) was used. The results obtained in young rats show that the distribution of delta opioid receptors is different in the various brain areas examined; these receptors appear to be maximally concentrated in the frontal poles, anterior and posterior cortex; lower concentrations were found in the other structures considered. Kd (dissociation constant) for the delta sites was found very similar in all areas. The distribution of delta opioid receptors in the brain of 24-month-old rats was similar to that observed in young animals; this result was surprising in view of the fact that aging modifies the number of other types of brain opioid receptors (mu and kappa).

Aging↗
PubMed1992

Effects of ovarian hormones on brain opioid binding sites in castrated female rats.

These experiments were performed to analyze whether treatments of ovariectomized female rats with ovarian steroid regimens able to induce either an increase (positive feedback effect) or a decrease (negative feedback effect) of serum levels of luteinizing hormone (LH) have some impact on the characteristics of mu-opioid binding sites in circumscribed areas of the brain. The increase of serum levels of LH elicited by a treatment with estradiol benzoate (EB) plus progesterone (P; positive feedback effect) was accompanied by a significant decrease in the number of mu-binding sites in the hypothalamus and in the corpus striatum. The decrease in serum levels of LH induced by a treatment with EB alone (negative feedback effect) brought about a significant increase of the number of mu-binding sites in the thalamus and in the hippocampus. These results seem to suggest that the release of LH induced by EB plus P may involve a decrease of hypothalamic mu-binding sites. Apparently, the inhibitory effect on LH release exerted by EB alone does not involve any change of the density of these binding sites in the hypothalamus.

Animals↗
PubMed1992

Antiproliferative effects of luteinizing hormone-releasing hormone agonists on the human prostatic cancer cell line LNCaP.

Highly potent LH-releasing hormone (LHRH) agonists have been recently introduced in therapy for the treatment of the carcinoma of the prostate, an androgen-dependent pathology. These peptides are believed to act mainly by inhibiting the pituitary-testicular axis and, consequently, by reducing testosterone levels. The recent observation that binding sites for LHRH analogs are present on prostatic tumor tissue suggests that these drugs could also act directly on the tumor. To verify this hypothesis, the effects of two potent LHRH agonists [Zoladex (Z) and Buserelin (B)] have been studied on the proliferation of the human prostatic cancer cell line LNCaP (lymph node carcinoma of the prostate). LNCaP cells were treated for 9 days with different doses of either Z or B (concentrations from 10(-12)-10(-6) M). Both analogs significantly inhibited cell proliferation at doses between 10(-9)-10(-6) M. The antiproliferative action of the two LHRH agonists was shown to be dose dependent, with IC50 values of 0.82 and 1.79 nM for Z and B, respectively. A similar treatment with B was without any significant effect on the proliferation of a mouse embryo fibroblast cell line (Swiss 3T3), which was used as a nontumoral control. The inhibitory action of both LHRH agonists (10(-8) M) on LNCaP cell proliferation was completely antagonized by the simultaneous treatment of the cells with a potent LHRH antagonist (Nal-Arg-LHRH; 10(-8) M); when given alone at the dose selected, the antagonist did not affect cell growth. These results clearly suggest that the antiproliferative effect of LHRH agonists on LNCaP cells may be mediated by specific receptors. The presence of binding sites for [125I]B was consequently demonstrated on the membranes of LNCaP cells cultured in a medium containing charcoal-stripped fetal calf serum, i.e. in the absence of steroids. The affinity of these binding sites for the ligand was lower than that observed for the same receptors on rat pituitary membranes. To clarify the mechanism of the antiproliferative action of the LHRH agonists, the effects of both Z and B on the incorporation of [3H]thymidine and [14C]methionine into LNCaP cells were investigated. During a short incubation period (3 h), the two LHRH agonists rapidly inhibited [3H]thymidine incorporation into the cells. The same treatment did not affect the incorporation of [14C]methionine into proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Agents↗
PubMed1991

Testosterone and postnatal ontogenesis of hypothalamic mu ([3H]dihydromorphine) opioid receptors in the rat.

Brain opioids modulate the activity of the hypothalamo-pituitary complex by binding to specific receptors which have been subdivided at least into 3 subclasses (mu, kappa, delta, etc). mu-Receptors and their ligands seem to be particularly involved in the control of gonadotropin and prolactin release. It is known that the neuroendocrine system, as well as the brain opioid systems and their receptors, are not fully mature at birth; it is also known that the postnatal maturation of many brain machineries is under the control of androgens secreted by the developing testes. Consequently, it has been investigated whether the presence or the absence of testosterone at time of birth may induce changes of the binding characteristics of hypothalamic mu-opioid receptors. The experiments have been performed by evaluating the maximal binding capacity (Bmax, an index of the number of receptors), and the affinity constant (Ka) of the specific mu-ligand dihydromorphine in hypothalamic plasma membrane preparations derived from normal male rats, normal female rats, male rats orchidectomized 2 days after birth and female rats treated 2 days after birth with 1.25 mg of testosterone propionate. Animals belonging to the 4 groups were killed at days 16, 26 and 60 of age. The results obtained show that, at 16 days of age, in the 4 groups of rats the number of hypothalamic mu receptors is identical. At 26 days a significant increase in the number of mu-receptors occurs in normal female animals, while their levels remain similar to those found at 16 days in the other 3 groups of animals. At 60 days of age, the number of mu-receptors in normal females remains elevated, while the number of mu-receptors increases to reach normal female levels in the hypothalamus of neonatally castrated males. At 60 days, there were no changes in normal males or in androgenized females. The variations here reported took place without any change of the Ka of dihydromorphine for the mu-receptors. These data show a sexual dimorphism of hypothalamic mu-receptors and suggest that their ontogenetic development may be linked to the presence or the absence of androgens at time of birth.

Animals↗
PubMed1991

Antibodies against the 59 kDa polypeptide of the N. crassa 8-10 nm filaments immunodetect a 59 kDa polypeptide in specialized rat epithelial cells.

P59Nc is a polypeptide associated with bundles of cytoplasmic and nuclear filamentous structures of 8-10 nm of diameter in Neurospora crassa cells. It is immunologically unrelated to both higher and lower eucaryotic tubulin and actin proteins and is detected weakly by the anti IFA monoclonal antibody. We analyze here the immunological relationship between P59Nc and intermediate filament (IF) mammalian proteins by using anti P59Nc, anti keratin, anti vimentin and anti IFA antibodies. Anti P59Nc antibodies detected a 59 kDa polypeptide from rat and bovine tissues which copurifies with polypeptides of the IF family. Neither P59Nc nor the 59 kDa rat polypeptide were recognized by anti keratin or anti vimentin antibodies. Immunostaining of rat tongue sections with anti P59Nc antibodies showed that the 59 kDa rat polypeptide is present in the cortical cytoplasm of suprabasal epithelial cells. The results indicate that P59Nc shares common antigenic determinants with a still uncharacterized 59 kDa polypeptide from mammalian tissues which have extractability and immunological properties similar to those of IF polypeptides and shows a tissular distribution and a cellular localization similar but distinguishable from keratins.

Animals↗
PubMed1991

Salvage chemotherapy for ovarian cancer recurrence: weekly cisplatin in combination with epirubicin or etoposide.

From December 1986 to April 1990, 40 consecutive ovarian cancer patients who relapsed after response to cisplatin-based chemotherapy regimens were treated with seven courses of weekly cisplatin, in combination with epirubicin or etoposide. The overall response rate obtained with the intensive schedule was 60% and the complete response rate was 25%; median duration of response was 7 months and median survival time, 13.5 months. Responsive cases seem to have longer survival; a prognostic factor for response to salvage treatment and longer survival is the disease-free interval after the first-line chemotherapy. Weekly cisplatin as intensive treatment was very well tolerated and showed acceptable toxicity in both the combination protocols with epirubicin or etoposide.

Adult↗
PubMed1991

Modulation of the binding characteristics of hypothalamic mu opioid receptors in rats by gonadal steroids.

Recent evidence suggests that the effects of the opioids on gonadotropin release may depend on the endocrine status existing in the experimental animal. In the brain, the effects of the opioids are exerted through the interaction with different classes of opioid receptors (mu, delta, kappa, etc.). Among these, the mu receptors appear to be particularly relevant to the control of gonadotropin secretion. Different groups of experiments have been performed in the rat in order to analyze whether changes of circulating levels of sex steroids may have an impact on the binding characteristics of hypothalamic mu opioid receptors, as evaluated by a receptor binding assay performed on plasma membrane preparations, using [3H]dihydromorphine as a mu ligand. In a first series of experiments, it has been observed that the ontogenesis of hypothalamic mu opioid receptors is different in male and in female rats: the concentration of mu sites, similar in animals of the two sexes at 16 days of age, increases in females, but not in males, between day 16 and day 26 of life. This sexual difference persists in 60-day old animals, when the brain is fully mature. It has also been observed that the pattern of maturation of hypothalamic mu receptors can be reversed by neonatal castration of males and by neonatal testosterone treatment of females. In a second series of experiments, it has been shown that in the hypothalamus of regularly cycling female rats the concentration of mu receptors varies during the different phases of the estrous cycle. In particular, a rather high density of mu sites during diestrus day 2 and the morning of the day of proestrus was found; this is followed by a progressive decline during the afternoon of the day of proestrus and the day of estrus, with a minimum value of the concentration of mu receptors being recorded in the first day of diestrus. These fluctuations seem to be linked to the physiological changes of serum levels of ovarian steroids: in fact, in a third series of experiments, it has been found that the positive feedback effect on LH release, exerted by the treatment of ovariectomized female rats with estrogens plus progesterone, is accompanied by a significant decrease of the concentration of hypothalamic mu opioid receptors; treatments with estrogens alone, able to induce a negative feedback effect on LH secretion, are not associated with modifications of hypothalamic mu receptors. These data seem to indicate that hypothalamic mu receptors may be involved in the positive but not in the negative feedback control of LH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Risk factors for epithelial ovarian tumours of borderline malignancy.

A case-control study was conducted on 91 cases with histologically-confirmed borderline ovarian tumours and 237 control subjects in hospital for acute non-gynaecological, hormonal or neoplastic disease. Women reporting three or more births, compared to nulliparae, had a relative risk (RR) estimate of 0.6, but this finding was not statistically significant (95% confidence interval (CI): 0.2-1.4). The risk of borderline tumours increased, although not significantly, with later age at first birth: compared to women reporting first birth at age 24 or before, the RRs were 1.3 and 1.7 in those reporting respectively their first birth at age 25-29 and 30 years or more. No significant relationship emerged between borderline ovarian cancer and age at menarche, menopausal status and lifelong menstrual pattern. Cases tended to report a later age at menopause than controls, but the trend in risk was not statistically significant. Nine cases (9.9%) and 68 controls (24.9%) reported oral contraceptive use: compared with never users the multivariate RR for ever users was 0.3, and the risk dropped with duration of use to 0.2 in users for two years or more (chi 2 (1) trend = 12.70, p less than 0.001). This study provides epidemiological evidence of a pathogenetic continuum between borderline and invasive ovarian tumours.

Adult↗
PubMed1991

Hypothalamic opiatergic tone during pregnancy, parturition and lactation in the rat.

The concentrations of beta-endorphin have been shown to change in the rat brain during pregnancy and lactation. This study has been performed in order to analyze whether also brain opioid receptors might undergo significant modifications during these two physiological situations. The maximal binding capacity (Bmax) and the constant of affinity (Ka) of the mu-subpopulation of opioid receptors have been evaluated in the hypothalami of female rats at different stages of pregnancy (7, 15 and 22 days), on the day of parturition (12-18 h after delivery) and 6-8 days postpartum (both in lactating and in nonlactating animals). Female rats killed on the day of estrus served as controls. The receptor binding assay has been performed utilizing [3H]-dihydromorphine [( 3H]-DHM) as the ligand for the mu-opioid receptors. Hypothalamic concentrations of beta-endorphin as well as serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin have also been evaluated by radioimmunoassay. The results showed that the concentration of hypothalamic mu-opioid receptors increased during pregnancy, being significantly higher than in the controls at days 15 and 22 of gestation. After delivery, the concentration of these receptors returned towards control values, regardless on whether the animals were lactating or not. The Ka values of [3H]-DHM for the mu-receptors did not change significantly in the different groups of experimental animals. Hypothalamic beta-endorphin content showed a modest though not significant increase at the end of gestation (day 22) and returned to control values 12-18 h after delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗