Search PubMed⌕ Search

Biomedical subjects

F Piva

Publications and source records attributed to F Piva.

At least 19 recordsLinked to original sources
PubMed1999

Improved dissolution behavior of fenbufen by spherical crystallization.

Fenbufen is an analgesic, antipyretic and anti-inflammatory drug that is characterized by poor water solubility, a defect increased by very low wettability. Poor water solubility, particularly at low pH, could decrease absorption in the upper part of the gastrointestinal tract, which would be inconvenient for good bioavailability. Different spherical crystallization processes have been considered as methods to improve fenbufen dissolution behavior. A two-solvent system, in the presence of a bridging liquid, is the only method capable of producing spherical fenbufen crystals. In a first step, fenbufen solubility was considered in different solvents. The drug crystals formed were typically needle shaped. This characteristic was considered as a favorable parameter to obtain spherical crystals. After the selection of the best fenbufen solvent, several ratios of solvent (S)-nonsolvent (NS) (tetrahydrofuran [THF]-demineralized water) were studied. The addition of a bridging liquid (isopropyl acetate) improved spherical crystallization. The results from this method were reproducible batch to batch. The spherical crystals obtained showed a clear improvement in dissolution capacity, probably due to better wettability. Dissolution studies were then carried out on these spherical crystals stored for 1 month at different relative humidities (RHs). The dissolution profiles remained unchanged.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Expression of prostacyclin receptors in luteinizing hormone-releasing hormone immortalized neurons: role in the control of hormone secretion.

PGs of the E series are involved in the control of LHRH secretion. The present experiments were conducted to clarify whether PGI2 (prostacyclin) might be also involved in such a control, using multiple methodological approaches on immortalized LHRH-secreting neurons. A RT-PCR procedure to detect mouse PGI2 receptor (IP) messenger RNA was first applied, and the results obtained showed the presence of a specific transcript in two cell lines of immortalized LHRH neurons (GT1-1 and GN11 cell lines). Receptor binding assays on membrane preparations from GT1-1 cells showed the presence of a single specific and saturable class of binding sites (Kd = 4.6 nM; 10,000 sites/cell) for [3H]iloprost, a stable analog of PGI2. Competition experiments showed that the binding sites labeled by [3H]iloprost possess the pharmacological characteristics of IP receptors. In functional studies, PGI2 and its analogs, iloprost and cicaprost, were able to stimulate LHRH release from the GT1-1 cells with elevated potencies (EC50 = 0.6-4.3 nM); PGE1 was only slightly less active (EC50 = 28.5 nM), whereas PGE2, considered the major PG involved in LHRH secretion, was poorly effective (EC50 = 921 nM). The relative potencies (EC50) of these compounds in stimulating the intracellular accumulation of cAMP were in line with their LHRH-releasing activities. In conclusion, these results indicate that immortalized LHRH-secreting neurons express IP receptors through which PGI2 may exert relevant effects on LHRH release.

Animals↗
PubMed1998

Biological effects of prolonged exposure to ELF electromagnetic fields in rats: III. 50 Hz electromagnetic fields.

Groups of adult male Sprague Dawley rats (64 rats each) were exposed for 8 months to electromagnetic fields (EMF) of two different field strength combinations: 5microT - 1kV/m and 100microT - 5kV/m. A third group was sham exposed. Field exposure was 8 hrs/day for 5 days/week. Blood samples were collected for hematology determinations before the onset of exposure and at 12 week intervals. At sacrifice, liver, heart, mesenteric lymph nodes, bone marrow, and testes were collected for morphology and histology assessments, while the pineal gland and brain were collected for biochemical determinations. At both field strength combinations, no pathological changes were observed in animal growth rate, in morphology and histology of the collected tissue specimens (liver, heart, mesenteric lymph nodes, testes, bone marrow), and in serum chemistry. An increase in norepinephrine levels occurred in the pineal gland of rats exposed to the higher field strength. The major changes in the brain involved the opioid system in frontal cortex, parietal cortex, and hippocampus. From the present findings it may be hypothesized that EMF may cause alteration of some brain functions.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Age-induced decrease of glycoprotein Po and myelin basic protein gene expression in the rat sciatic nerve. Repair by steroid derivatives.

The data here reported show that the gene expression of the glycoprotein Po and of the myelin basic protein, the major components of myelin in the peripheral nervous system, dramatically decreases with ageing in the sciatic nerve of normal male rats. A one-month treatment with dihydroprogesterone, the 5alpha-reduced derivative of progesterone, is able to partially restore the fall in Po gene expression occurring in the sciatic nerve of aged male rats, without significantly modifying the gene expression of the myelin basic protein. In cultures of neonatal Schwann cells (the peripheral nervous system elements involved in the synthesis of myelin), the addition of progesterone and of dihydroprogesterone significantly increases Po gene expression; the 3alpha-reduced metabolite of dihydroprogesterone, tetrahydroprogesterone proved to be even more effective. These data suggest that the effect of progesterone is linked to its conversion into dihydroprogesterone and especially into tetrahydroprogesterone, since Schwann cells possess the 5alpha-reductase-3alpha-hydroxysteroid dehydrogenase system. The data provide the first demonstration that ageing decreases the gene expression of two major components of the peripheral myelin in the sciatic nerve; they also show that this phenomenon may be partially reversed by progesterone derivatives, which might act by stimulating Po gene expression in the Schwann cells.

20-alpha-Dihydroprogesterone↗
PubMed1998

Mechanism of action of interleukin-1 in modulating gonadotropin secretion. In vivo and in vitro studies

To obtain further information on the mode of action of interleukin (IL)-1 in modulating gonadotropin secretion, a series of in vivo and in vitro studies has been performed with the beta-isoform of IL-1. IL-1 beta injected in a lateral ventricle of 3-week-castrated female rats resulted in the expected decrease in serum levels of gonadotropins luteinizing hormone (LH), and follicle-stimulating hormone (FSH), accompanied by a decrease in the number of LH-releasing hormone (LHRH) receptors. These results may indicate that the inhibition of gonadotropin release may result from a decrease in the number of LHRH pituitary receptors either through a direct effect on the pituitary or by modulating the release of LHRH from hypothalamic neurons able to induce a reduction in pituitary LHRH receptors. In vitro studies using the GT1-1 cell line, which specifically produces and secretes LHRH, demonstrated that IL-beta stimulates LHRH release but does not influence intracellular levels of LHRH mRNA. These results seem to indicate that IL-1 beta may act at several levels of the nervous machinery leading to gonadotropin secretion, with a series of effects more complex than previously anticipated.

Journal Article↗
PubMed1997

LHRF, LHRH, GnRH: what controls the secretion of this hormone?

In the present study, the possible direct effects of opioids on the release of LHRH have been studied utilizing the GT1-1 cell model. It has been shown that only opioid agonists which bind to delta receptors bring about a significant inhibition of the release of LHRH, when this is stimulated by forskolin- or PGE2. The effects of delta opioid agonists are dose-dependent, and are reversed by the delta specific antagonist naltrindole. If one assumes that the GT1-1 cells represent a good model for the study of LHRH-secreting neurons, the obvious conclusion from these data is that endogenous opioid peptides may influence LHRH secretion also by acting directly on LHRH-secreting neurons. In another study it has been shown that GT1-1 cells possess high affinity-low capacity binding sites for estradiol and androgens. Moreover, a two-fold induction of androgen-binding sites has been observed after treatment of GT1-1 cells with estradiol, indicating that estrogen receptors are functional. The present observations suggest that gonadal steroids might influence LHRH release acting directly on the cells which manufacture and release the hypothalamic hormone. In order to evaluate the possible existence of a humoral communication between glial cells and LHRH-secreting neurons, two different approaches have been used: (a) GT1-1 cells were co-incubated with purified cultures of type 1 astrocytes; (b) GT1-1 cells were exposed to the conditioned medium (CM, untreated or submitted to different experimental procedures) where type 1 astrocytes were grown for 24 h. In both sets of experiments LHRH was measured by RIA in the incubation media of GT1-1 cells. The data show that short periods of either co-culture or exposure to previously frozen or heated CM significantly increase the release of LHRH from the GT1-1 cells. The stimulatory effect on LHRH release appears to be specific for type 1 astrocytes. Surprisingly, fresh CM proved to be inactive; this suggested that the factor(s) involved needed to be 'activated'. Since it is known that TGF beta may be liberated from its supporting proteins by freezing or heating, the effects of TGF beta and of a TGF beta-neutralizing antibody were analyzed. The stimulatory effect exerted by the frozen CM was completely abolished by the antibody, while TGF beta 1 proved able to significantly increase LHRH release from GT1-1 cells. The present data unequivocally show that type 1 astrocytes in culture release some principle(s), probably TGF beta, able to stimulate LHRH release from the LHRH-producing GT1-1 cell line. To the authors' knowledge, the present data provide the first clear-cut demonstration that the glia may directly intervene in the control of LHRH release via the secretion of humoral factors.

Animals↗
PubMed1997

Effects of epidermal growth factor on the [3H]-thymidine uptake in the SK-N-SH and SH-SY5Y human neuroblastoma cell lines.

The studies on the factors that regulate the biology of the neuroblastoma cell lines may offer important information on the development of tissues and organs that derive from the neural crest. In the present paper we study the action of epidermal growth factor (EGF) on two human neuroblastoma cell lines: SK-N-SH which is composed at least of two cellular phenotypes (neuroblastic and melanocytic/glial cells), and its pure neuroblastic subclone SH-SY5Y. The results show that EGF (10 ng/ml) significantly stimulates the incorporation of [3H]-thymidine in the SK-N-SH cells only in the presence of fetal bovine serum (FBS) (control = 58,285 +/- 9327 cpm; EGF = 75,523 +/- 4457, p < 0.05). Such effect is not observed in the presence of a chemical defined medium, that is, in the absence of FBS (control = 100,997 +/- 4375; EGF = 95,268 +/- 4683; NS) In the SH-SY5Y cells the EGF does not modify the incorporation of [3H]-thymidine either in the presence of 10% of BFS (control = 113,838 +/- 6978; EGF = 119,434 +/- 9441; NS) or in its absence (control = 46,197 +/- 3335; EGF = 44,472 +/- 3493; NS). The results here reported suggest that: a) EGF may affect the proliferation of cells derived from a primary human neuroblastoma; b) this is evident by the EGF-induced increase of [3H]-thymidine incorporation in SK-N-SH cells; c) it is required the presence of other growth factors, present in the FBS, for the mitogenic action to be accomplished; d) since the pure neuroblastic SH-SY5Y cell line are refractory to the EGF, the effects observed in SK-N-SH cells probably occur on the melanocytic/glial cell subpopulation.

Epidermal Growth Factor↗
PubMed1996

Antiprogestins inhibit the binding of opioids to mu-opioid receptors in nervous membrane preparations.

The present study showed that the glucocorticoid/progesterone antagonists, 17 beta-hydroxy-1 1 beta-(4-dimethylamino-phenyl-1)-17-(prop-1-ynyl)estra-4,9-dien+ ++-3-one (RU486) and 17 beta-hydroxy-11 beta-(4-dimethylamino-phenyl-1)-17-(propan-3-ol)estra-4,9-dien-3-o ne (ZK 98299), inhibit the binding of labeled dihydromorphine to mu-opioid receptors present on membrane preparations derived from rat and mouse brain, as well as from human neuroblastoma cells. The inhibitory effect of RU486 was dose-dependent and linked to a decrease of the affinity of labeled dihydromorphine to the mu-opioid receptors. Kinetic experiments have shown that RU486 induces a decrease of the association rate constant (k + 1) of dihydromorphine. RU486 also proved able to dissociate the dihydromorphine-mu-opioid receptor complex, although at a rate slower than that exhibited by unlabeled dihydromorphine. Finally, the addition of NaCl (100 mM) to the incubation buffer induced a 50% decrease of the inhibitory effect of RU486. A 6-day treatment of neuroblastoma cells with RU486 eliminated the inhibitory effect morphine exerts on the intracellular accumulation of cyclic AMP induced by prostaglandin E1. These results indicate that RU-486 may interact with brain mu-opioid receptors in vitro, by decreasing the affinity of opioid ligands.

Analgesics↗
PubMed1995

Effects of steroids on the brain opioid system.

The experiments reported here add further evidence in support of the view that sex steroids may influence the binding characteristics of brain opioid receptors. In particular, it has been shown that: (a) the number of mu-opioid receptors varies in the hypothalamus of regularly cycling female rats according to the different phases of the estrous cycle, which are characterized by fluctuations of circulating levels of sex steroids; (b) the number of mu-opioid receptors decreases in the hypothalamus and in the corpus striatum when ovariectomized rats are submitted to treatments with estradiol and progesterone able to induce a "positive" feedback effect on LH release. A treatment with estrogen alone able to induce a "negative" feedback effect on LH release brings about an increase of the number of mu-opioid receptors in the thalamus and in the hippocampus; (c) in addition to the mu-receptors, receptors of the delta type may also be involved in the control of gonadotropin secretion; recent results here presented indicate that a line of immortalized hypothalamic cells (GT1 cells), which synthesize and secrete LHRH, present delta opioid receptors on their membranes; these are apparently involved in the control of LHRH release from these cells.

Alprostadil↗
PubMed1995

Characterization of functional opioid delta receptors in a luteinizing hormone-releasing hormone-producing neuronal cell line.

Endogenous opioids participate in the regulation of gonadotropin secretion through an influence on the release of the hypothalamic LHRH. However, it is not clear whether opioids exert a direct effect on LHRH-producing neurons or interfere with other systems able to influence LHRH release. A neuronal LHRH-producing cell line (GT1) developed recently provides a good model to study the mechanisms controlling LHRH release. In the present study, the presence of opioid receptors on a subclone of GT1 cells (GT1-1) has been investigated. A specific and saturable binding of the 3H-labeled nonselective opioid ligand diprenorphine ([3H]DIP) was detected by a receptor binding assay on both intact GT1-1 cells and crude membrane preparations obtained from these cells. Analysis of saturation curves revealed that [3H]DIP apparently binds to a single class of sites with a Kd of 0.2 nM and a binding capacity of 125 fmol/mg protein, corresponding to approximately 20,000 sites/cell. Selective displacement of the binding of [3H]DIP to GT1-1 cells by [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin, [D-Pen2,D-Pen5]enkephalin (DPDPE), and U50488H, which are selective ligands, respectively, for mu-, delta-, and kappa-receptors, was also evaluated. Only the specific delta-ligand DPDPE produced a significant inhibition of the binding of [3H]DIP. [D-Ala2,N-Me-Phe4,Gly5-ol]Enkephalin and U50488H were totally ineffective. The inhibitory effect of the agonist DPDPE on the binding of [3H]DIP was decreased by the presence of sodium ions, a typical characteristic of the binding of agonists to opioid receptors. Finally, it has been observed that treatment with prostaglandins E1 and E2 produces a dramatic increase in cAMP accumulation in GT1-1 cells, and DPDPE is highly effective in suppressing this effect. On the basis of these results, it is possible to postulate the presence of functional delta-opioid receptors on GT1-1 cells. By extrapolation, one might suggest that endogenous opioids may affect LHRH neurons by two mechanisms: a direct one, acting via delta-receptors, and an indirect one, through the activation of neurons impinging on the LHRH system, which uses mu-receptors.

Animals↗
PubMed1995

Inhibition of luteinizing hormone-releasing hormone secretion by delta-opioid agonists in GT1-1 neuronal cells.

The endogenous opioids play a major role in regulation of the secretion of hypothalamic LHRH. However, it is not clear whether opioids exert a direct effect on LHRH neurons or interfere with other neuronal systems impinging on the cells synthesizing LHRH. The neuronal LHRH-producing cell line GT1 provides a new model to evaluate which signals may directly modify LHRH release. In a previous paper it has been reported that opioid-binding sites of the delta-type are present in a clone of the GT1 cells (GT1-1). In the present study, the possible effects of opioids on the release of LHRH were studied in GT1-1 cells. The results obtained show that only the addition of opioid agonists that bind to delta-receptors brings about a significant inhibition of forskolin- or prostaglandin E2-stimulated LHRH release in GT1-1 cells. The effect of the delta-opioid agonist [D-Pen2,D-Pen5]enkephalin is dose dependent and is reversed by the universal opioid antagonist naltrexone and the delta-specific antagonist naltrindole. No effect of opioid agonists or antagonists was observed in unstimulated cells. These results suggest that opioids may control the release of LHRH also, acting directly on LHRH-producing neurons.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
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

Preparation and properties of a therapeutic inter-alpha-trypsin inhibitor concentrate from human plasma.

Inter-alpha-trypsin inhibitor (ITI) is a serine protease inhibitor found in human plasma. Its antiprotease activity is due to bikunin which is effective in various types of experimental shock and pancreatitis. Therefore ITI, which releases bikunin by proteolytic cleavage, could be of therapeutic interest. A method for the large-scale isolation of ITI from human plasma is described. ITI was purified from the prothrombin complex concentrate (PCC) by diethylaminoethyl-Sepharose fast-flow chromatography followed by a chromatographic step on immobilized heparin designed to remove C4, factor X and protein C. With this procedure, which was performed under mild conditions, a homogeneous preparation of native ITI was obtained, as demonstrated by electrophoretic and chromatographic analyses. ITI maintained its biological activity, as exhibited by its specific antitryptic activity of 420 +/- 65 IU/g. In order to decrease or eliminate the risk of transmission of viral disease due to lipid-enveloped viruses, the process incorporated a solvent-detergent treatment. Animal studies on the final product revealed no adverse side-effects in terms of toxicity, thrombogenicity or hypotension. This preparation appears suitable for therapeutic evaluation in animal experimental models.

Alpha-Globulins↗
PubMed1994

Effect of ovariectomy on the binding characteristics of hypothalamic mu opioid receptors in the rat.

The present experiments have been performed to analyze whether ovariectomy, performed in adult female rats, might influence the binding characteristics of hypothalamic mu binding sites. To this purpose, different groups of ovariectomized females have been killed by decapitation 1, 3, 7, 15 and 21 days after surgery, and the binding characteristics (Bmax and Kd) of the mu receptors have been determined in their hypothalami. Dihydromorphine was used as a specific mu ligand. The data obtained have been compared with those derived from the hypothalami of adult female rats in the morning of proestrus, when the density of hypothalamic mu opioid receptors reaches its highest concentration. Blood from trunk vessels was also collected for the evaluation of serum LH levels by radioimmunoassay. The results obtained have shown that one day after ovariectomy, the number of hypothalamic mu opioid binding sites is as high as that found in proestrus animals. The number of these binding sites tends to decrease on days 3, 7 and 15 after surgery. On day 21 after gonadectomy, the number of mu binding sites results to be significantly lower than that observed in the hypothalami of intact female rats in the morning of proestrus and in the hypothalami of female animals castrated since one day. The value of the Kd did not show any variation on days 1, 3, 15 and 21; however, a significant increase of this parameter (which indicates a decrease of the affinity of the ligand for its receptors) was observed on day 7 after ovariectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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

Human leucocyte elastase (HLE) preferentially cleaves the heavy chain H2 of inter-alpha-trypsin inhibitor (ITI).

Inter-alpha-trypsin inhibitor (ITI) is a complex protein containing two heavy polypeptide chains (H1 and H2) and a light chain, which in the free state is known as bikunin. In vitro cleavage of ITI with different proteases releases bikunin, but does not abolish the antitryptic activity. To study the mechanism of bikunin release, ITI was incubated with human leucocyte elastase (HLE). The resulting ITI fragments were characterized by (i) their electrophoretic and chromatographic behavior. (ii) their immunological reactivity towards antibodies specific for each of the heavy chains H1 and H2, and (iii) their N-terminal sequences. Our results demonstrate that the H2 heavy chain of ITI is particularly sensitive to HLE, and that early cleavage products (M(r)-values 120-150,000) consist of H1 linked to bikunin. A scheme is proposed for the mechanism for ITI degradation.

Alpha-Globulins↗
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↗