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Biomedical subjects

M Maggiolini

Publications and source records attributed to M Maggiolini.

31 records · Page 2Linked to original sources

A time course study on the "in vitro" effects of T3 and testosterone on androgen and estrogen receptors in peripuberal primary rat Sertoli cells.

The effect of Tri-iodothyronine (T3) administration leading to the precocius differentiation of Sertoli cell in prepuberal rats has been previously shown. The functional maturation of Sertoli cells is associated with changes in androgen metabolism. We have recently demonstrated that T3 influences androgen metabolism in Sertoli cells by inhibiting aromatase activity and reduces drastically the ER contents in peripubertal hypothyroid rats. To better understand the role of T3 in modulating steroid action on Sertoli cells, we performed a time course study evaluating the in vitro effects of T3 and testosterone (T) on androgen (ARs) and estrogen (ERs) receptor content in Sertoli cells isolated from two weeks old Wistar rats. ARs and ERs basal levels did not change during the time course study indicating that the exposure to culture medium per se did not affect either receptor type. After 24 hrs of incubation with either T3 or T, a decrease of ERs in both nucleus and cytosol was observed. Such a decrease was augmented by the simultaneous administration of both hormones. ARs displayed a different temporal pattern in the two cellular compartments and exhibited an earlier rise in the cytosol induced by either T3 or T. At 36 hrs, ARs were significantly enhanced in both compartments in response to either T or T3 exposure while combined hormonal treatment caused an additive increase compared with the single treatment group. As a consequence of the opposite behaviour pattern displayed by ARs and ERs, the ratio between total ARs and ERs contents was increased after 24 hrs of exposure to hormonal treatment. To evaluate if treatments performed induced a functional maturation of Sertoli cells, transferrin levels in culture medium were measured. The increase of this protein paralleled that of ARs content as well as that of ARs/ERs ratio. This study demonstrates that thyroid hormone induces a progressive increase of (AR)/(ER) ratio in the differentiating Sertoli cells bringing them to a prevalent androgen dependency along their functional maturation.

Animals↗

Effect of oestradiol and insulin on the proliferative pattern and on oestrogen and progesterone receptor contents in MCF-7 cells.

In a long-term experiment MCF-7 cells showed an exponential proliferation rate in fetal calf serum while they become quiescent in growth-factor- and steroid-free serum. The mitogenic activity of this cell line was increased by oestradiol and insulin, exposure to both hormones showing a synergic effect. These mitogen-mediated effects are inhibited by genistein a phytoestrogen which, by itself at the doses used, did not affect either the basal proliferation rate or the total protein content. Immunoblotting and Scatchard analysis reveal respectively that insulin increases the oestrogen receptor (ER) content and its binding capacity. The presence of genistein decreases the ER content and completely abolishes the binding capacity of this protein. Insulin is able to increase progesterone receptor (PR) levels while, in the presence of genistein, the above-reported effect was completely abolished. On the basis of the latter data the authors suggest that insulin is able to affect the phosphorylation status of ER and PR, inducing functional changes in both proteins, although this was in the absence of their natural ligands. Indeed, the presence in the medium of a tyrosine kinase inhibitor such as genistein could substantially decrease both ER and PR levels in these cells.

Breast Neoplasms↗

GH secretion in thalassemia patients with short stature.

The physiological role of GH secretion on growth retardation remains to be elucidated especially in patients with beta-thalassemia. In the present study, we investigated IGF-1 circulating levels as well as GH release following GHRH alone or combined with some inhibitors of somatostatin: pyridostigmine and arginine. In thalassemic patients lower IGF-1 circulating levels appear to be negatively correlated with both aspartate aminotransferase and alanine aminotransferase as well as with ferritin circulating levels indicating a probable role of hepatic hemosiderosis in IGF-1 production. The authors however suggest that reduced IGF-1 secretion is not the main cause of growth retardation since this would have elicited an enhanced response of GHRH in the presence of a normal hypothalamic pituitary axis. In contrast, they noticed that GH response to GHRH when expressed as area under the curve was lower in thalassemic patients compared to controls. The combination of GHRH with either pyridostigmine or arginine induced a GH secretion in thalassemics which was comparable to that of controls. The results of this study lead to conclude that the alteration of GH secretion is due, in such patients, to an increased somatostatin activity.

Adolescent↗

Follow-up study on the effects of thyroid hormone administration on androgen metabolism of peripubertal rat Sertoli cells.

The inhibitory effect of triiodothyronine (T3) given in early postnatal life on Sertoli cell proliferative activity, leading to their precocious terminal differentiation, has been demonstrated previously. However, data concerning the role of thyroid hormone on androgen metabolism of Sertoli cells during the same period are still lacking. In this study we performed a time-course investigation on the effects of T3 treatment on testosterone metabolism in Sertoli cells isolated from 2-, 3- and 4-weeks-old euthyroid rats. Triiodothyronine (3 micrograms/100 g body wt) was given ip., during the last week prior to sacrifice. Sertoli cells from all animal groups initially were cultured under basal conditions during the first 24 h and subsequently in the presence of testosterone (0.5 mumol/l) with or without T3 (1 nmol/l) for an additional 24 h. This treatment given to 2-week-old animals resulted in reduced testicular growth. As far as androgen metabolism is concerned, T3 in vivo and in vitro treatment in 2- and 3-week-old animals induced a lowering of dihydrotestosterone + 3 alpha-diol with an enhancement of the two other 5 alpha-reduced androgens. The effect was much less pronounced in the oldest group. In both 2- and 3-week-old treated rats a marked reduction of oestradiol was observed, which indicates an inhibition of aromatase activity, mainly in younger animals. This enzyme has been reported to be extremely active in Sertoli cells of rats (of the same strain) between the age of 5 and 20 days, but it decreases rapidly thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Endemic goiter in Calabria: etiopathogenesis and thyroid function.

An endemic goiter study was carried out in a vast territory of the Calabria region, including the provinces of Catanzaro and Cosenza. About 50% of 7231 school-children, aged between 6 and 12 years, examined in 34 villages, presented a thyroid enlargement. The high prevalence of goiter seems to be related to a moderate iodine deficiency intake indicated by a mild urinary iodine excretion (lower than 100 micrograms/g creatinine). In a few villages, in which a two year voluntary iodine prophylaxis was carried out, an increase in the urinary iodine excretion with a decreased goiter prevalence was observed. A slight increase in TT3, FT3 and TSH in one endemic area studied, compared to the control area, was also observed. These data suggest that an effective program of iodoprophylaxis is fundamental in this region as well.

Child↗

[Secondary hepatic hemochromatosis: diagnosis and quantification with 0.5 T magnetic resonance. Value and limitations].

Iron overload is a major cause of morbidity and mortality in thalassemia major patients. All chronic liver diseases may be associated with such endocrine symptoms as diabetes mellitus, testicular failure or hypothyroidism. We studied 15 thalassemic patients (12 men and 3 women; age range: 10-50 years, mean: 22.5 years). All patients received blood transfusions, but only some were treated with iron chelation. Seven patients were splenectomized. MRI was performed with an 0.5 T superconducting magnet, using SE T1- and T2-weighted and IR sequences. We used these data with Bloch's equation to calculate T1 and T2 values. Quantitative analysis was made by calculating signal intensity and relaxation times in 8 hepatic regions of interest: marked reduction in hepatic signal intensity and a negative relationship between T1 and serum ferritin (r = 0.646, p < 0.01) and between T2 and serum ferritin (r = 0.688, p < 0.01) were observed. Moreover, a negative relationship was found between hepatic signal intensity and aspartic aminotransferase (r = 0.524, p < 0.05). Our results confirm the value of MRI in the diagnosis and evaluation of hepatic iron overload but an accurate quantitative analysis can be made only when hepatic iron levels are between 1 and 2 mg/g of liver. Even though it is below statistical significance, the negative relationship between signal intensity and aspartic aminotransferase suggests that hepatic hemochromatosis can influence pituitary-thyroid axis and interfere with peripheral hormone metabolism.

Adolescent↗

The in vitro conversion of 3H androstenedione to testosterone and dihydrotestosterone in the adrenal gland of castrated male rat: influence of gonadal steroid administration.

In the present study we considered the effects of bilateral orchiectomy on the metabolism of androstenedione in the adrenal gland of the adult male rat. Adrenal glands of intact animals incubated in the presence of 3H androstenedione resulted in its conversion to testosterone and dihydrotestosterone (the two principal metabolites investigated). The value of the latter metabolite increased with the elapsing of time from castration despite the decrease of testosterone with respect to that observed in the sham operated rats of the same age. This effect is reversed in the presence of testosterone treatment with androstenedione and testosterone levels similar to those obtained in intact animals. Androstenedione adrenal metabolism is greatly lowered following the administration of dihydrotestosterone propionate, resulting in high substrate residue values with respect to untreated castrated rats. Contemporarily, testosterone metabolite value remains unchanged while the production of dihydrotestosterone is significantly lower. Finally a decrease of DHT was also encountered in the presence of estradiol benzoate. The above results clearly point to a progressive activation of the 5 alpha-reductase of the adrenal gland after castration utilizing androstenedione as substrate. The metabolic pathway leading to the production of dihydrotestosterone from androstenedione appears to be modulated differently following the administration of gonadal steroids.

Adrenal Glands↗

The in-vitro transformation of [3H]dehydroepiandrosterone into its principal metabolites in the adrenal cortex of adult castrated male rats and following steroid treatment.

The adrenal gland of castrated adult male rats metabolized [3H]dehydroepiandrosterone in vitro to delta 4-androsten-3,17-dione (4AD), testosterone, dihydrotestosterone (DHT) and 5 alpha-androstane-3,17-dione (5 alpha AD). Despite the low testosterone values, DHT and 5 alpha AD were higher 30 and especially 60 days after castration, with raised 4AD:testosterone and decreased testosterone:DHT ratios. The 5 alpha-reductase activity thus appears to increase with time after castration. Fourteen days after castration, 4AD was the only metabolite that was raised compared with intact animals, and testosterone was comparable in sham-operated and castrated rats. The administration of testosterone propionate to castrated rats restored testosterone values to those of intact rat adrenals, whereas 4AD values were greater. The administration of dihydrotestosterone propionate also yielded higher levels of 4AD, in the presence of a lower testosterone value. After administration of oestradiol benzoate, 4AD values were lower especially compared with the other hormone-treated groups, and there was an unexpectedly high testosterone value. These data indicate that the adrenal gland contributes to the production of androgens, as previously noted by Andò, Canonaco, Beraldi et al. (1988) who showed increased plasma 4AD and testosterone levels in adult male rats 30 days after castration. Furthermore, adrenal androgen production in castrated animals is differentially regulated by sex steroids.

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

The evaluation of androgen circulating levels following castration in adult male rats.

In the present study dehydroepiandrosterone (DHEA), androstenedione (A), testosterone (T) and dihydrotestosterone (DHT) plasma levels were determined in adult male rats five days, seven weeks and eleven weeks after orchiectomy and confronted, respectively, with rats 60 days old which were sacrificed 5 days, 7 weeks and 11 weeks after the sham-operation for orchiectomy. It was revealed that five days after castration A, T and DHT were decreased with respect to sham-operated rats. Seven and eleven weeks after orchiectomy only T remained lower. In all three groups of castrated animals the A/T ratio resulted augmented whereas T/DHT ratio resulted lower with respect to the sham-operated animals. Five days after castration DHEA plasma concentration was positively correlated to A levels and both androgens resulted negatively correlated to T plasma levels. Seven weeks after bilateral orchiectomy an inverse correlation appeared between DHEA/A ratio and T. This emphasizes the role of DHEA and A in maintaining testosterone circulating levels. Seven and eleven weeks following castration the A/T ratio was negatively related to the T/DHT ratio, indicating that A contributes to DHT plasma levels. In the second part of our study the effect of sex steroid administration was evaluated 7 weeks after castration. A linear correlation between DHEA and T circulating levels was obtained following the administration of T while treatment with oestradiol caused a significant increase of the DHEA/A ratio. The castrated animals that received DHT presented lower T circulating levels while the A/T ratio was significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Fructose, prostatic acid phosphatase and zinc levels in the seminal plasma of varicoceles.

The function of sex accessory glands in 95 varicocele patients was investigated by determining the fructose, prostatic acid phosphatase (PAP), and zinc levels in the seminal plasma. These biochemical substances are, in fact, markers of the seminal vesicles and prostate, respectively. It was observed that both the PAP and zinc levels were significantly lower (P less than .002) in varicoceles than in the control group, while both fructose and PAP levels were particularly low in a small subgroup of the older patients. The authors suggest that the impaired sex accessory gland functions could arise from decreased venous drainage in the vesico-prostatic plexus. The fructose/zinc ratio appears to be negatively related to sperm motility (r = .31, P = .01); this suggests that in varicocele the impaired sex accessory gland secretions could themselves influence the motility of ejaculated spermatozoa.

Acid Phosphatase↗

The evaluation of free-L-carnitine, zinc and fructose in the seminal plasma of patients with varicocele and normozoospermia.

The function of the epididymis and of the sex accessory glands have been investigated in a selected group of varicocele patients with normal sperm count. In the seminal plasma of these patients free-L-carnitine, fructose and zinc levels were determined as functional markers respectively of epididymis, seminal vesicles and prostate. Despite the unvaried free-L-carnitine and fructose levels, zinc levels were significantly lower (p less than 0.001) than in the control group. The Zn/F ratio, an index of the ratio between the prostatic and vesicular secretions, resulted also lower (p less than 0.01) with respect to the controls. The authors suggest that the impaired prostatic function could arise from the decreased venous drainage in the vesico-prostatic plexus. In the same patients sperm motility resulted significantly lower than in the controls, and was positively related to zinc levels (r = 0.44, p less than 0.01) and, to a higher degree, to the Zn/F ratio (r = 0.62, p less than 0.001). Our data show that in this selected group of varicocele patients with a not yet altered tubular epididymal unit, sex accessory gland secretions can influence, per se, the motility of the ejaculated spermatozoa.

Adult↗