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E Messi

Publications and source records attributed to E Messi.

17 recordsLinked to original sources
PubMed1997

Differential effects of low- and high-dose estrogen treatments on vascular responses in female rats.

In an attempt to study the mechanisms by which estrogens affect vascular responses, we utilized aortic preparations from intact and ovariectomized female rats receiving low- and high-dose subcutaneous estrogen treatments. Oil-treated, as well as male rats, served as controls. In ovariectomized females, low-dose 17-beta-estradiol injections (5 microg/kg daily for two days) affected the basal release of nitric oxide, as evaluated by concentration-related curves to superoxide dismutase and N(G)-Methyl-L-arginine acetate, which was found to be greater in 17-beta-estradiol-treated females compared to oil-treated females or males. Conversely, the nitric oxide-related vascular relaxation evoked by acetylcholine and sodium nitroprusside was unchanged. Prostacyclin production was also evaluated. Aortic rings from ovariectomized 17-beta-estradiol-treated females released significantly more prostacyclin than those from oil-treated females. These results point out a possible role for nitric oxide and prostacyclin in the vascular protection brought about by physiological levels of estrogens. When intact females were treated with high doses of ethynilestradiol (100 microg/Kg daily for one month), a component of contraceptive pills, either the basal release of nitric oxide, or acetylcholine-induced relaxation underwent a significant decrease. Likewise, the relaxant responses to sodium nitroprusside were impaired in the aortic rings obtained from ethynilestradiol-treated animals when compared to controls. Similarly, the amount of prostacyclin released from aortic tissues obtained from ethynilestradiol-treated animals was significantly reduced. These results may provide a possible explanation for the higher incidence of cardiovascular disease in women who take contraceptive preparations containing high doses of estrogens.

Acetylcholine↗
PubMed1997

Astrocyte-neuron interactions in vitro: role of growth factors and steroids on LHRH dynamics.

The data here reviewed, obtained with in vitro models, indicate that growth factors and steroids play a significant role in astrocyte-neuron interactions. Different designs have been adopted: (1) GT1-1 cells (a cell line derived from a mouse hypothalamic LHRH-producing tumor) were cocultured with type 1 rat astrocytes; and (2) GT1-1 cells were exposed to the conditioned medium (CM) in which type 1 rat astrocytes had been grown for 24 h. LHRH release and mRNA LHRH levels were measured respectively in the medium and in cell homogenates, at different time intervals (LHRH release, by RIA; LHRH mRNA by Northern blot analysis). The data obtained show that type 1 astrocytes secrete in the medium TGFbeta, which is able to modulate the release and the gene expression of LHRH in GT1-1 cells; and that one or more LHRH-degrading enzymes is/are present in the conditioned medium of type 1 astrocytes. A second part of the experiments have indicated that type 1 astrocytes are also able to affect, in different directions, the metabolism of testosterone and progesterone into their 5alpha-reduced metabolites occurring in the GT1-1 cells. In particular, it has been observed that the conversion of testosterone into DHT is decreased by the coculture with type 1 astrocytes, while the conversion of progesterone into DHP is increased by the same coculture conditions. Moreover, type 1 astrocytes are sensitive to steroid hormones, and in particular to the 5alpha-reduced metabolites of progesterone; this has been shown by analyzing the effects exerted by different steroids on the gene expression of the typical astrocyte marker GFAP.

Animals↗
PubMed1996

Transforming growth factor-beta and astrocytic conditioned medium influence luteinizing hormone-releasing hormone gene expression in the hypothalamic cell line GT1.

On the basis of our previous observations indicating that a principle [possibly transforming growth factor-beta1 (TGFbeta1)] secreted by type 1 astrocytes may increase the release of LHRH in the GT1 cell line, it was deemed of interest to analyze whether TGFbeta1 might influence LHRH gene expression in addition to LHRH release in GT1-1 neurons. The effects of TGFbeta1 on the levels of LHRH messenger RNA (mRNA) present in GT1-1 cells have been compared to those found after either coculture of these cells with type 1 astrocytes or exposure of GT1-1 cells to the conditioned medium in which type 1 astrocytes were grown for 24 h. The data obtained indicate that 1) TGFbeta1 increases LHRH mRNA levels 1 and 6 h after the beginning of treatment; longer exposures (24 h) bring about a decrease in LHRH gene expression; 2) a significant stimulatory effect of TGFbeta1 (1 and 6 h of exposure) is also evident on LHRH release; 3) the exposure to the conditioned medium of type 1 astrocytes is able to increase LHRH gene expression in GT1-1 cells at 1 h; LHRH mRNA levels show a small decrease after 6 h of exposure, which becomes more evident at 24 h; and 4) the coculture of GT1-1 cells with type 1 astrocytes is not able to modify LHRH mRNA levels at any time considered. The present data support the concept that glial cells are able to control, possibly through the release of TGFbeta, the gene expression of LHRH in hypothalamic neurons.

Astrocytes↗
PubMed1995

Type 1 astrocytes influence luteinizing hormone-releasing hormone release from the hypothalamic cell line GT1-1: is transforming growth factor-beta the principle involved?

The possible existence of a humoral communication between glial cells and LHRH-secreting neurons has been studied using the LHRH-secreting GT1-1 cell line and type 1 astrocytes. Two different designs have been adopted: 1) GT1-1 cells were coincubated with purified cultures of type 1 rat astrocytes, and 2) GT1-1 cells were exposed to the conditioned medium (CM) in which type 1 rat astrocytes had been grown for 24 h. LHRH was measured by RIA in the medium of the GT1-1 cell cultures at different time intervals. The data show that short periods (1, 3, and 6 h) of either coculture or exposure to previously frozen CM significantly increase the release of LHRH from the GT1-1 cells. However, more prolonged times of coculture (e.g. 2 and 5 days) or exposure to CM (e.g. 48 h) induce a significant decrease in the amount of LHRH in the medium. The stimulatory effect on LHRH release appears to be specific for type 1 astrocytes (either cortical or hypothalamic), because neither the CM of oligodendrocytes nor the CM of LNCaP cells (a cell line derived from a human prostatic cancer) possess stimulating activities. Heating the type 1 astrocyte-CM to 100 C for 10 min does not eliminate the ability of the CM to significantly increase the release of LHRH from GT1-1 cells at 1, 3, and 6 h. Because of the opposite effects encountered in the short and long term experiments, it was hypothesized that the CM might contain, in addition to LHRH-releasing principle(s), LHRH-degrading properties. Known amounts of standard LHRH were then added to type 1 astrocyte-CM, either untreated or submitted to heating at 100 C for 10 min. The amount of LHRH added to untreated CM decreases progressively; on the contrary, the amount of LHRH added to heated CM remains unchanged. These results confirm that one or more heat-sensitive enzymes able to degrade LHRH may be present in the type 1 astrocyte-CM. As previously mentioned, the experiments reported so far were performed using type 1 astrocyte-CM that had been kept frozen for various periods of time, before being tested for its LHRH-releasing activity. Surprisingly, fresh CM proves to be inactive, whereas heated CM is effective; this suggests that the factor involved might be activated by the two opposite experimental procedures.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

The anterior pituitary gland as a possible site of action of kainic acid.

The purpose of the present study was to analyze the direct effect of kainic acid (KA), an agonist of L-Glutamate, on the secretion of LH and FSH from anterior pituitary (AP) of male rats perifused in vitro. At low concentrations (1 microM), KA was able to stimulate the release of both gonadotropins from AP of 50-day-old male rats, but the response to subsequent stimuli was markedly impaired. This, however, was not due to a neurotoxic action of KA, but seemed rather suggestive of a down-regulation or desensitization of KA receptors. The stimulatory action of KA on LH and FSH secretion was age-dependent, since the agonist was completely ineffective on the AP of 75-day- and 18-month-old male rats. DNQX (6,7-dinitroquinoxaline-2,3-dione), a specific antagonist of the KA receptor subtype, was able to block the KA-induced gonadotropin secretion; similarly, AP-5 (2-amino-5-phosphonovalerate), a competitive NMDA receptor antagonist, prevented the stimulatory effect of KA on LH and FSH release. An interaction between the opiatergic and the excitatory aminoacid (EAA) systems emerged from the observation that pulses of KA applied to AP of 50-day-old male rats during a continuous perifusion with a medium containing morphine (5 microM) failed to increase gonadotropin secretion. These results indicate that KA can, at low concentrations, directly stimulate LH and FSH secretion by acting at AP level; this effect disappears with progression of age, and might be exerted both through NMDA and non-NMDA receptor subtypes. Finally, the results provide evidence that opioids and excitatory aminoacids might influence gonadotropin secretion from AP by acting in opposite directions.

2-Amino-5-phosphonovalerate↗
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↗
PubMed1991

Sex steroids and the control of LHRH secretion.

Gonadal steroids are important hormonal signals that regulate the activity of LHRH synthesizing and releasing neurons. Aside from a direct effect through the feedback mechanisms exerted at hypothalamic and/or anterior pituitary level, gonadal steroids may modify the rhythmic LHRH release by modulating other systems affecting LHRH neurons. 1. In ovariectomized E2-treated female rats, progesterone is able to evoke LHRH release from the perifused hypothalamus without affecting LH and FSH release. 2. Excitatory amino acids (EAA) and their related analogs (NMDA and kainate) are known to stimulate LH release in young rats. When tested in a perifusion system on hypothalamic and anterior pituitary tissues, they differentially stimulate the release of LHRH (NMDA) and of LH (KA); their effect on both structures is markedly reduced following orchidectomy. It appears that gonadal steroids might exert a facilitatory action on the neurosecretory activity of LHRH neurons as well as a modulatory influence on the effect of EAA.

Amino Acids↗
PubMed1990

Ageing does not influence the ultrashort feedback control of GnRH secretion in vitro.

Evidence indicates that long and short feedback systems are altered in the aged male rat. Data also indicate the existence of an ultrashort feedback mechanism controlling GnRH secretion. The present experiments were performed to test whether the ultrashort feedback control of GnRH is operating also in old male rats. Mediobasal hypothalami of 18-month-old male rats were perifused in vitro either in the presence or in the absence of a GnRH agonistic analogue (Buserelin: [D-Ser(TBU)6,Des-Gly10]GnRH ethylamide) and stimulated with 5-min pulses of K+ (for a total of six pulses) in order to test their ability to release GnRH. The hypothalamic fragment was exposed to the GnRH analogue either for a part of the experimental period (at the beginning or at the end) or for the whole duration of the perifusion. In both cases, the presence of the analogue diminished or totally abolished the responses to K+ stimulation. This is in line with the results obtained in young animals. The data suggest that the ultrashort feedback mechanism controlling GnRH release is normally functioning also in aged male rats despite the fact that other types of feedback mechanisms (long and short loop) are substantially altered.

Aging↗
PubMed1988

Antihormonal activities of 5 alpha-reductase and aromatase inhibitors.

The problem of developing androgen antagonists has been tackled so far only by synthesizing steroids able to displace testosterone and other androgens from their specific receptor sites. The observation that testosterone has to be converted intracellularly either to 5 alpha-reduced metabolites (DHT, 3 alpha-diol, etc.) or to estrogens, in order to become fully active on androgen-dependent structures (both central and peripheral), has opened the possibility of creating molecules which prevent these conversions, and which could then block the actions of testosterone. The availability of these new compounds has allowed a better understanding of the selective physiological role of each of the metabolites of testosterone, and to provide the basis for the development of new hormone antagonists to be used in those clinical conditions for which an inhibition of the actions of testosterone is foreseen. The usefulness of these enzyme inhibitors is underlined by some examples described in this paper. The results obtained may permit the formulation of the following conclusions: (1) The conversion of testosterone to its 5 alpha-reduced metabolites occurring in the neuroendocrine structures may represent an essential step for the appearance of the inhibitory feedback effect testosterone exerts on LH secretion; (2) Testosterone exhibits its negative feedback effect on FSH secretion as such and not following the local aromatization to estrogens; (3) Testosterone exerts its effect on the intrahypothalamic stores of LHRH acting as such and not following its local conversion either to 5 alpha-reduced metabolites or to estrogenic molecules; (4) Some of the new enzyme inhibitors (e.g. 4-OH-A) may represent an interesting tool for the treatment and/or the prevention of BPH and possibly of other androgen-dependent diseases (prostate carcinoma, acne etc.), as shown by their ability to prevent the in vitro conversion of testosterone to its 5 alpha-reduced metabolites both in the normal prostate of the rat and in the human BPH tissue.

Animals↗
PubMed1988

Testosterone and the control of hypothalamic GnRH.

The aim of the present study was to test the hypothesis that the restoring effect of testosterone on hypothalamic GnRH stores in orchidectomized 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 micrograms/rat daily); or TP (2 mg/rat daily) plus TMX (50 or 200 micrograms/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.

Animals↗
PubMed1987

Aging and the hypothalamo-pituitary-testicular axis in the rat.

Several experiments have been performed in order to clarify the mechanisms through which aging in male rats brings about profound modifications of the neuroendocrine system (reduced pulsatile secretion of LH and FSH, decreased serum levels of gonadotropins and testosterone, etc.). (1) It has been found that the number of mu opioid receptors decreases significantly in the hypothalami of old male rats; the substitution therapy with testosterone is ineffective in increasing the number of mu opioid receptors. These data suggest that the decrease of hypothalamic mu opioid receptors is not due to a decline of serum testosterone levels, but appears to be an independent phenomenon. (2) K opioid receptors increase significantly in the amygdala and in the thalamus of old male rats. These results show that aging, in addition to mu receptors, affects also the number of K receptors in selected areas of the brain. The increase of the number of K receptors in the amygdala might have some bearing on the decrease of serum gonadotropins observed in aged rats, since the amygdala is involved in the nervous circuitry influencing the hypothalamo-pituitary-gonadal axis. (3) The study of the release of LHRH from the hypothalamus of old male rats with an in vitro perfusion system shows that the release of the hormone is comparable in young and old animals, both in basal and in K+ stimulated conditions. These results indicate that the hypothalamus of old male rats retains the capacity of releasing LHRH both in basal and in stimulated conditions. (4) It has been observed that the number of LHRH receptors at the level of the anterior pituitary is significantly reduced in old male rats. This finding might explain the low serum levels of gonadotropins and testosterone in aged rats, due to a lack of an adequate response of the pituitary to hypothalamic LHRH.

Aging↗
PubMed1987

In vitro release of luteinizing hormone-releasing hormone from the hypothalamus of old male rats.

The present experiments tested the ability of the hypothalamus of old male rats to release LHRH in vitro. Mediobasal hypothalami (MBH) of 18-month-old and 6-month-old male rats were perfused for a total of 5 h and 5 min; the amounts of LHRH released, both in basal conditions and after stimulation with high extracellular K+ (110 mM, applied for 5 min every 30 min), were measured in the effluent. Our results show that the basal secretion of LHRH from the perfused MBH of young and old male rats is quantitatively similar. Moreover, the MBHs of young and old animals are capable of responding to the repeated administration of a K+ stimulus with repeated bursts of LHRH hypersecretion. From a quantitative point of view, the MBHs of old animals respond to the K+ stimulus in a fashion similar to that found in younger animals; even if the responses to K+ of the hypothalami of old animals appear to be somewhat lower than those of the hypothalami of younger animals, the differences recorded were not significant. LHRH content (as measured by RIA) of the MBH before the perfusion period was similar in young and old animals. At the end of the experiment, the content of LHRH of the perfused hypothalamus was not significantly different in the old and young groups. Serum and intrapituitary levels of LH and FSH were significantly lower in 18-month than in 6-month-old animals. These data suggest that the alterations of the function of the hypothalamic-pituitary-gonadal complex observed in aged male rats are not due to an intrinsic age-related defect of LHRH-synthesizing neurons.

Aging↗
PubMed1987

Ultrashort feedback control of luteinizing hormone-releasing hormone secretion in vitro.

The present experiments were performed to clarify whether LHRH might inhibit its own secretion via an ultrashort feedback mechanism acting directly on the hypothalamus. Using an in vitro system, mediobasal hypothalami (MBHs) of adult male rats were perifused in either the presence or absence of a LHRH agonistic analog [D-Ser(TBU)6,Des-Gly10] LHRH ethylamide shown not to cross-react in the LHRH RIA. In the first series of experiments, six MBHs per chamber were initially perifused with control medium and submitted to two K+ stimulations (110 mM) for 5 min every 30 min; the control medium was then replaced by medium containing the LHRH analog (5 microM), and three additional K+ pulses were applied. In the second series of experiments, a single MBH per chamber was exposed for the duration of the experiments to either control medium or medium containing the LHRH analog (5 microM). In both cases, pulses of K+ were applied to the tissue. The amounts of endogenous LHRH released both under basal conditions and after K+ stimulation were measured in the effluent (1 ml every 5 min) with a specific RIA. The results show that the LHRH analog inhibits basal secretion of endogenous LHRH from the MBH, and diminishes or abolishes the response to K+ stimulations. The specificity of the inhibitory effect exerted by the LHRH analog on LHRH secretion was shown by the inability of TRH to mimic the effect of the LHRH analog. The data are consistent with the hypothesis that LHRH, acting at a hypothalamic level, might participate in the control of its own release via an ultrashort feedback mechanism.

Animals↗
PubMed1984

Inhibin.

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Animals↗
PubMed1983

Influence of adrenalectomy and ovariectomy on gonadotrophin secretion.

In order to gain additional information on the effects exerted by adrenal hormones on gonadotrophin secretion, adult female rats have been submitted concomitantly to adrenalectomy and ovariectomy; ovariectomized animals with intact adrenals served as controls. Serum levels and pituitary concentrations of LH and FSH have been measured on post-operation days 1, 2, 7, 14 and 28. It has been found that ovariectomy, when performed alone, induces a progressive but delayed release of LH and a rapid and constant release of FSH. Ovariectomy exerts only minor effects on the concentrations of pituitary LH, while providing a strong stimulus to the intrapituitary accumulation of FSH. Adrenalectomy, superimposed on ovariectomy, advances the release of LH, and at the 4-week interval, increases serum levels of this gonadotrophin to well above those found in animals submitted only to ovariectomy; the absence of the adrenals does not significantly alter the release of FSH. Adrenalectomy, added to gonadectomy, strongly facilitates the accumulation of LH in the anterior pituitary, but decreases the resynthesis of FSH. In conclusion, these data suggest that one or more factors of adrenal origin may: (1) inhibit the release of LH without affecting the release of FSH; (2) prevent the post-gonadectomy accumulation of LH in the anterior pituitary and facilitate the re-accumulation of FSH.

Adrenalectomy↗