Biomedical subjects

F Larrea

Publications and source records attributed to F Larrea.

At least 37 records · Page 2Linked to original sources

PubMed2000

The oestrogenic effects of gestodene, a potent contraceptive progestin, are mediated by its A-ring reduced metabolites.

Gestodene (17 alpha-ethynyl-13 beta-ethyl-17 beta-hydroxy-4, 15-gonadien-3-one) is the most potent synthetic progestin currently available and it is widely used as a fertility regulating agent in a number of contraceptive formulations because of its high effectiveness, safety and acceptability. The observation that contraceptive synthetic progestins exert hormone-like effects other than their progestational activities, prompted us to investigate whether gestodene (GSD) administration may induce oestrogenic effects, even though the GSD molecule does not interact with intracellular oestrogen receptors (ER). To assess whether GSD may exert oestrogenic effects through some of its neutral metabolites, a series of experimental studies were undertaken using GSD and three of its A-ring reduced metabolites. Receptor binding studies by displacement analysis confirmed that indeed GSD does not bind to the ER, whereas its 3 beta,5 alpha-tetrahydro reduced derivative (3 beta GSD) interacts with a relative high affinity with the ER. The 3 alpha,5 alpha GSD isomer (3 alpha GSD) also binds to the ER, though to a lesser extent. The ability of the A-ring reduced GSD derivatives to induce oestrogenic actions was evaluated by the use of two different molecular bioassays: (a) transactivation of a yeast system co-transfected with the human ER alpha (hER alpha) gene and oestrogen responsive elements fused to the beta-galactosidase reporter vector and (b) transactivation of the hER alpha-mediated transcription of the chloramphenicol acetyl transferase (CAT) reporter gene in a HeLa cells expression system. The oestrogenic potency of 3 beta GSD was also assessed by its capability to induce oestrogen-dependent progestin receptors (PR) in the anterior pituitary of castrated female rats. The results demonstrated that 3 beta GSD and 3 alpha GSD were able to activate, in a dose-dependent manner, the hER alpha-mediated transcription of both the beta-galactosidase and the CAT reporter genes in the yeast and HeLa cells expression systems respectively. In both assays the 3 beta derivative of GSD exhibited a significantly greater oestrogenic effect than its 3 alpha isomer, while unchanged GSD and 5 alpha GSD were completely ineffective. Neither 3 beta GSD nor 3 alpha GSD exhibited oestrogen synergistic actions. Interestingly, the pure steroidal anti-oestrogen ICI-182,780 diminished the transactivation induced by 3 beta GSD and 3 alpha GSD in the yeast expression system. Furthermore, administration of 3 beta GSD resulted in a significant increase of oestrogen-dependent PR in the anterior pituitaries of castrated rats in comparison with vehicle-treated animals. The characteristics of the 3 beta GSD-induced PR were identical to those induced by oestradio benzoate. The overall results demonstrate that 3 beta GSD and its 3 alpha isomeric alcohol specifically bind to the ER and possess a weak intrinsic oestrogenic activity, whereas unmodified GSD does not. The data contribute to a better understanding of the GSD mechanism of action and allow the hypothesis to be advanced that the slight oestrogenlike effects attributable to GSD are mediated by its non-phenolic, tetrahydro reduced metabolites.

Animals↗

PubMed1999

Effects of IGF-I on 1,25-dihydroxyvitamin D(3) synthesis by human placenta in culture.

The aim of the present study was to assess the effects of insulin-like growth factor I (IGF-I) upon the synthesis of 1, 25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] by human placenta trophoblasts in culture. Cytotrophoblastic cells obtained from normal term human placentae were cultured in Dulbecco's modified Eagle's medium with HEPES and glucose (DMEM-HG) during 72 h and further incubated in serum-free DMEM-F12 in the presence of IGF-I prior to the addition of [(3)H]-25-(OH)D(3) used as a precursor. The results showed that 2 h preincubation time with IGF-I was required for maximal production of [(3)H]-1,25-(OH)(2)D(3). Cultures in the presence of increasing concentrations of IGF-I (0-6.5 nmol/l), added 2 h before incubation with the labelled substrate, resulted in a dose-dependent response increment of [(3)H]-1,25-(OH)(2)D(3) production with a maximal conversion rate at the dose of 2.6 nmol/l. Higher doses of IGF-I did not result in further stimulatory effects. Co-incubations in the presence of cycloheximide significantly (P < 0. 0001) inhibited the IGF-I-mediated effects upon [(3)H]-1, 25-(OH)(2)D(3) production. Identity of putative [(3)H]-1, 25-(OH)(2)D(3) produced by human placenta was confirmed by spectral and receptor binding analysis. These results demonstrate the ability of cultured human syncytiotrophoblast cells to convert 25-(OH)D(3) to 1,25-(OH)(2)D(3) and suggest a local protein-dependent regulatory effect of IGF-I upon this biotransformation.

Calcifediol↗

PubMed1998

Sex hormone-binding globulin stimulates chorionic gonadotrophin secretion from human cytotrophoblasts in culture.

The effects of sex hormone-binding globulin (SHBG) on the secretion of human chorionic gonadotrophin (HCG) and cAMP by cultured human cytotrophoblasts were investigated. Cytotrophoblasts obtained from normal term placentae were cultured in serum-free medium with or without the addition of human SHBG. The presence of SHBG in the medium increased the release of HCG and the accumulation of cAMP. Ligand-free SHBG was able to raise both HCG and cAMP concentrations and the maximal response was observed with 1 nM of the steroid-binding globulin. Addition of either oestradiol or 5alpha-dihydro-testosterone (DHT) to cultures previously incubated with SHBG in a final molar ratio of 1:10 resulted in a further increase of HCG and cAMP concentrations. This effect was blocked when cultured placental cells were exposed to SHBG that was previously saturated with DHT or when incubated in the presence of steroids only. The results of the present study provide evidence for the in-vitro regulation of HCG secretion by SHBG and further support the concept that this steroid-binding protein may act as a mediator of steroid action at the cellular level. Finally, the increase in cAMP suggests that SHBG receptor located in the surface of syncytiotrophoblast membranes is coupled to adenylate cyclase as part of the G-protein receptor family. Our results may provide new insights into the biological implications of extracellular steroid-binding proteins as well as new perspectives on the endocrinology of pregnancy.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1998

Differential effects of glycosylated and non-glycosylated porcine prolactin on estradiol and progesterone secretion by rat granulosa cells in culture.

BACKGROUND: The objective was to better understand the interactions between prolactin and ovarian function. METHODS: The effects of two variants of porcine prolactin (pPRL) on estradiol (E2) and progesterone (P4) production by rat granulosa cells in culture were studied using granulosa cells obtained from large preovulatory follicles of pregnant mare serum gonadotropin (PMSG)-treated immature Sprague-Dawley rats. Cultures were performed in the absence or presence of hCG (0.1 IU/ml) and different concentrations of either glycosylated and non-glycosylated (g-pPRL and ng-pPRL, respectively) pPRL. RESULTS: Dose-response studies showed that maximal stimulation occurred in all instances with g-pPRL at the dose of 10 ng/mL during the 72-h treatment period. In the case of E2, the maximal response was obtained in hCG-stimulated cultures, whereas the response of P4 was higher in cultures stimulated with g-pPRL in the absence of hCG. In a similar manner, the non-glycosylated form of pPRL increased, although to a lesser extent, the secretion of P4 only in those cultures incubated in the absence of hCG. In contrast to these observations, ng-pPRL was about twice as active than the glycosylated form on the stimulation of growth of Nb2 lymphoma cells. CONCLUSIONS: These data point out that glycosylation is involved in the differential effects of pPRL on ovarian steroidogenesis and support the role of carbohydrates in the structural-functional polymorphic nature of the hormone.

Animals↗

PubMed1997

A bioactive 60-kilodalton prolactin species is preferentially secreted in cultures of mitogen-stimulated and nonstimulated peripheral blood mononuclear cells from subjects with systemic lupus erythematosus.

We have evaluated the production of PRL by human peripheral mononuclear cells (PBMNC) from normal subjects and patients with systemic lupus erythematosus (SLE). Conditioned medium prepared from basal and Con-A-stimulated PBMNC was assessed for the presence of PRL-like by its ability to stimulate growth of PRL-responsive Nb2 rat lymphoma cells. In the presence or absence of Con-A, SLE PBMNC secrete significantly higher (P < 0.001) amounts of bioactive PRL-like species than normal cells. Growth of Nb2 cells by conditioned medium was inhibited with specific antiserum to human PRL. Western blotting using a polyclonal antibody to human PRL revealed a single 60-kDa PRL-like species in both normal and SLE PBMNC extracts, the immunoreactivity of which was preferentially found in SLE subjects. With the use of reverse transcription-PCR an expected 633-bp band was observed, and its similarity to pituitary PRL was further confirmed by Southern blot analysis with human PRL complementary DNA as a probe. We conclude that a high molecular mass PRL-like species is synthesized and secreted by PBMNC, and patients with SLE have an increased secretion of lymphocyte-derived PRL-like material.

Adolescent↗

PubMed1997

Biologically active steroid and thyroid hormones stimulate secretion of sex hormone-binding globulin by human term placenta in culture.

In this study, the influence of steroid and thyroid hormones and epidermal growth factor on the production of SHBG by placental tissue explants was investigated. Explants of trophoblastic tissue obtained from normal term placentas were cultured for 48 h in serum free culture medium, and then for an additional 24 h period in the presence or absence of various concentrations of either estradiol (0.25-5 nM), testosterone (0.5-500 nM), triiodothyronine (0.01-100 nM) or EGF (2-40 microM), respectively. Human SHBG concentration in culture media was estimated on each day by specific two-site time-resolved fluoroimmunometric assay and the results expressed as pmol/mg tissue protein. Binding characteristics and molecular structure of secreted SHBG were determined by [3H]5 alpha-DHT binding assays and Western blot analysis, respectively. Estradiol and triiodothyronine but not testosterone increased significantly (p < 0.05 vs. control) the secretion of SHBG into the culture media. Addition of EGF did not significantly change the production of SHBG at the various concentrations studied. [3H] 5 alpha-DHT binding assays and Western blot analysis of placental SHBG resulted in identical binding affinities (Kd 2.0 +/- 0.16 x 10(-9)M) and molecular structure to those obtained in serum from normal pregnant women. These findings support and extend previous observations by our laboratory indicating that SHBG gene is expressed in the placenta and provide further evidence on the hormonal regulatory characteristics of this steroid-binding protein in cultured placenta.

Epidermal Growth Factor↗

PubMed1996

The prolactin inhibition of follicle-stimulating hormone-induced aromatase activity in cultured rat granulosa cells is in part tyrosine kinase and protein kinase-C dependent.

The inhibitory actions of prolactin on gonadal steroidogenesis have been reported in different species and under a variety of experimental approaches. In this study, the mechanisms of the in-vitro effects of human prolactin (hPRL) on human follicle stimulating hormone (hFSH)-induced aromatase activity were determined using cultured granulosa cells from diethylstilboestrol (DES)-primed immature rats. Human PRL caused a dose-dependent decrease in hFSH-induced 17 beta-oestradiol production, even when cells were cultured in the presence of a cAMP analogue (8-Br-cAMP). These effects of hPRL appeared to be specific, since addition of an anti-rat PRL receptor monoclonal antibody (mAb) mimicked the hPRL inhibitory effect upon steroidogenesis in rat granulosa cells. In order to assess the importance of tyrosine kinase and protein kinase-C activation in the hPRL inhibitory effects upon oestrogen biosynthesis, cells were cultured in the presence of kinase inhibitors. The results showed that addition of genistein or staurosporine (a tyrosine kinase and protein kinase-C antagonist respectively) to cultured granulosa cells resulted in potent inhibition of hPRL actions upon hFSH-induced aromatization in a dose-dependent manner. These observations suggest that tyrosine kinase and protein kinase-C activation are involved in the biochemical events leading to hPRL inhibitory effects at the gonadal level.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1995

Genetic variations in human testosterone-estradiol binding globulin.

The human testosterone-estradiol-binding globulin (hTeBG) is a plasma heterogeneous glycoprotein with high affinity for a number of circulating steroid hormones. The heterogeneity originates from differential glycosylation of a common protein precursor. Analysis of desialylated hTeBG by isoelectric focusing (IEF) has revealed that microheterogeneity could be partly attributed to variability in sialic acid content or rearrangement of amino acid composition. We have studied this possibility by the analysis of desialylated serum hTeBG by Western blotting of proteins previously separated on IEF-gels. Two distinct well-defined IEF patterns were identified. The most frequent consisted of two major IEF-bands of equal color intensity. The other pattern consisting of four IEF-bands was present in only 5.55% of the total serum samples analyzed. Family studies showed that these phenotypes were autosomally inherited with a simple Mendelian transmission and allele frequencies had an excellent agreement between the observed and expected phenotypes. Androgen affinity constants and serum concentrations of hTeBG variant were similar to those of normal hTeBG. Molecular analyses of each of the exons of hTeBG gene by denaturing gradient gel electrophoresis revealed the presence of a point mutation in exon 8. The studies presented herein confirm and extend previous reports on the existence of structural variants of hTeBG. In addition, the mutation reported in this study is probably the same as that recently identified within numerous ethnic groups throughout the world, thus further supporting the concept of a two allele gene worldwide concoding hTeBG.

Female↗

PubMed1995

Evidence for an altered luteinizing hormone sensitivity to naloxone in pathological hyperprolactinaemia.

OBJECTIVE: The underlying mechanisms involved in the pathogenesis of amenorrhoea in hyperprolactinaemic states still remain unclear. Conflicting information exists on the role of endogenous opiates on gonadotrophin disturbances in this pathological condition. In this study we have undertaken a detailed investigation of LH and PRL secretion before and during administration of naloxone, an opioid receptor blocker, in hyperprolactinaemic women with or without ovarian function in order to assess the role of ovarian steroids upon naloxone induced LH and PRL release. DESIGN: Five anovulatory and six ovulatory subjects with hyperprolactinaemia were studied before and during naloxone infusion. Five normo-prolactinaemic ovulatory subjects were included as controls. All ovulatory subjects were studied during the luteal phase of a menstrual cycle. Blood was sampled every 10-20 minutes over a 16-hour period on two alternate days. On study day 1 (control day), subjects received two sets of saline infusion every 6 hours and one saline bolus at the beginning of the seventh hour; on study day 3 (naloxone day), they received a saline infusion during the first 6 hours, an intravenous bolus of naloxone (20 mg) at the beginning of the seventh hour and then a continuous naloxone infusion (1.6 mg/hour) during the ensuing 6 hours. Pituitary LH responsiveness and reserve were assessed on both study days by the subsequent administration of 5 and 95 micrograms of GnRH 4 hours before the completion of each sampling period. MEASUREMENTS: Serum concentrations of LH, PRL, oestradiol and progesterone were determined by radioimmunoassay. LH and PRL pulse detection and characteristics were analysed by the Cluster program. RESULTS: Serum PRL levels in hyperprolactinaemic anovulatory and ovulatory subjects were significantly elevated above the normal range. Oestradiol and progesterone serum levels during the luteal phase in women with hyperprolactinaemia and regular menses were similar to those in control ovulatory subjects. Mean LH concentrations increased during naloxone infusion (P < 0.05) in ovulatory hyperprolactinaemia and controls, whereas PRL increased (P < 0.05) only in the group of control subjects. LH pulse amplitude and pulse interval were increased by naloxone (P < 0.05) in all the ovulatory subjects, with no significant changes in anovulatory hyperprolactinaemic women. PRL pulse characteristics were modified significantly by naloxone only in the control group. On day 1, GnRH administration increased LH in all groups, whereas a consistently lower pituitary LH response was observed after naloxone (day 3). Serum PRL levels significantly increased after GnRH administration on day 1 only in normal women, whilst on day 3 this GnRH-dependent PRL releasing effect was significantly attenuated. CONCLUSIONS: The absence of stimulatory effects of naloxone on LH in anovulatory hyperprolactinaemia implies that endogenous opiates do not play a significant role in the mechanisms governing hypothalamic amenorrhoea in this syndrome. The results in subjects with ovulatory hyperprolactinaemia suggest the existence of an active role of ovarian steroids on naloxone induced LH release. These data, along with those previously reported in normal women throughout the menstrual cycle, are consistent with the concept that sex steroid hormones contribute to the underlying mechanisms involved in the opioidergic control of LH and PRL release. Whether PRL by itself or through other non-opioid neuroendocrine pathways alters the hypothalamic-gonadotroph unit still requires further investigation.

Adolescent↗

PubMed1995

Molecular characterization of a genetic variant of the steroid hormone-binding globulin gene in heterozygous subjects.

Steroid hormone-binding globulin in human serum displays different isoelectric focusing (IEF) patterns among individuals, suggesting genetic variation in the gene for this extracellular steroid carrier protein. Analysis of allele frequencies and family studies suggested the existence of two codominant alleles of the gene. Subsequent determination of the molecular basis of a variant of the gene was carried out using DNA from homozygous individuals from a single Belgian family. It was of interest to characterize other variant individuals to determine whether all variants identified by IEF phenotyping were caused by the same mutation or whether other mutations occurred in the gene in different populations. Previous studies identified Mexican subjects who were heterozygous for the variant IEF phenotype. Denaturing gradient gel electrophoresis was used to localize the mutation in these subjects and to purify the variant allele for DNA sequence analysis. The results show that the mutation in this population is identical to that identified in the Belgian family, and no other mutations were detected in the gene. These data represent the first analysis of steroid hormone-binding globulin gene variation in heterozygous subjects and further support the conclusion of biallelism of the gene worldwide.

Base Sequence↗

PubMed1994

Cellular and humoral immune parameters in women with pathological hyperprolactinemia before and during treatment with bromocriptine.

PROBLEM: Experimental and clinical evidence has suggested an immunostimulatory effect of prolactin and that bromocriptine, an inhibitor of prolactin release, counteracts the actions of prolactin on the immune system. The aim of this study was to determine the impact of elevated serum prolactin levels on the immune system in patients with pathological hyperprolactinemia. METHOD: For this purpose, parameters of the cellular and humoral immune system were studied in six women with prolactinomas and one with idiopathic hyperprolactinemia. Studies were performed when serum prolactin concentrations were high as well as during different phases of the menstrual cycle when prolactin levels had been normalized through treatment with bromocriptine. RESULTS: Hyperprolactinemic subjects, when compared with six age-matched normal women, had significantly higher percentages of total lymphocytes and CD2+ cells. Elevation of CD4+ cells was also observed although to a lesser extent. Bromocriptine-treated patients, when compared with normal women were characterized by increased numbers of total lymphocytes and CD4+ cells, decreased percentage of CD8+ cells, and increased concentrations of serum IgM. These last two findings were also significantly different when compared to those observed in hyperprolactinemia. CONCLUSION: In this study we have described the changes on cellular and immune parameters in patients with hyperprolactinemia before and during bromocriptine therapy, which support the links of communications between the immune and endocrine systems in humans.

Adolescent↗

PubMed1993

Evidence that human placenta is a site of sex hormone-binding globulin gene expression.

The presence of an androgen-binding component in placenta was investigated in vitro using a tissue culture system of human placental explants. Explants of trophoblastic tissue from normal term placentas were kept in culture under appropriate conditions for at least 48 h in a serum-free medium. The existence of an androgen-binding protein was explored by binding assays, immunohistochemistry studies and Northern blot analyses of placental mRNA. Steady-state polyacrylamide gel electrophoresis and Scatchard plot analyses revealed the presence of a high affinity specific binding component for 5 alpha-dihydrotestosterone in cultured placenta. Immunohistochemical studies performed on intact placenta and on Percoll-gradient purified trophoblastic cells demonstrated the presence of specific immunoreactivity in the cytoplasm of syncytial cells. Northern blot analyses of placental mRNA showed a single hybridizable 32P-labeled human sex hormone-binding globulin (SHBG) cDNA band of approx. 1.6 kb which was identical in size to that obtained with liver mRNA. The results strongly suggest the placenta as an origin of SHBG and point out this tissue as an additional site of SHBG synthesis during pregnancy.

Blotting, Western↗

PubMed1993

Serum pattern of different molecular forms of prolactin during normal human pregnancy.

In this study, the molecular heterogeneity of prolactin was analysed in serum from normal women throughout pregnancy. Lectin affinity chromatography and denaturing polyacrylamide gel electrophoresis under reducing and non-reducing conditions, followed by Western blotting and immunostaining were used to resolve and identify the molecular variants of prolactin. During the first trimester, large molecular forms (64 and 53 kDa) and those corresponding to glycosylated and non-glycosylated prolactin (25 and 23 kDa, respectively) were present either under reducing or non-reducing conditions. The 64 and 23 kDa were the predominant species at this stage of gestation. As pregnancy progressed, the 64 kDa variant, which did not bind to concanavalin A, decreased until disappeared at the third trimester of gestation. The unbound/bound ratio of serum prolactin to concanavalin A increased only at the third trimester; however, the relative proportions of concanavalin A-bound prolactin did not show statistically significant changes along the gestational period. The results demonstrated the occurrence of changes in the heterogeneity of prolactin during gestation and further confirmed previous observations that various forms of non-glycosylated prolactin are indeed the predominant species in serum from normal women throughout pregnancy.

Adult↗

PubMed1992

Prolactin size variants during pregnancy in women with ovulatory hyperprolactinemia: characterization by isoelectric focusing and lectin affinity chromatography.

Previous studies from this laboratory have demonstrated the occurrence of important changes in PRL size heterogeneity in women with ovulatory hyperprolactinemia during gestation. A similar observation has been made, in normal women, for glycosylated PRL, which shows a progressive decrease as pregnancy progresses. In this study we decided to investigate the contribution of G-PRL on PRL heterogeneity throughout gestation in women with ovulatory hyperprolactinemia. Serum samples obtained throughout gestation were analysed by SDS-PAGE followed by immunoblotting and by isoelectric focusing of gels as well. The results indicated that, independent of the stage of pregnancy, the relative amounts of G-PRL as compared with the nonglycosylated form of the hormone remained quite constant. In addition, isoelectric focusing analyses of serum samples consistently resulted in an identical isoelectric point of PRL throughout all of the gestational period. These results suggested that changes in the relative proportions of PRL size species during pregnancy were not correlated with the degree of PRL glycosylation. Moreover, these observations further extended and supported the concept that the occurrence of PRL size heterogeneity depends mainly on thiol-disulfide interchange mechanisms, among PRL molecules, at the pituitary level.

Adult↗

PubMed1992

Hyperprolactinemia inhibits natural killer (NK) cell function in vivo and its bromocriptine treatment not only corrects it but makes it more efficient.

We studied NK cell function in eight patients with pathological hyperprolactinemia by measuring 51Cr release by K562 cells exposed to their mononuclear cells and found it decreased compared to normal controls (P less than 0.01). Bromocriptine (BrC) treatment corrected NK function but also made it more efficient at 12:1 than at 25:1 or 50:1 effector:target ratios (ANOVA; P = 0.01). The study of NK cell function in agarose revealed that its decrease in hyperprolactinemia is due to their low active binding to target cells, active killing, and recycling capacity. BrC tended to correct them but also increased recycling capacity to levels higher than those of controls (P less than 0.05). Sequential studies in three hyperprolactinemic patients before and after BrC showed correction of NK function within 1 week but its increased efficiency at the 12:1 effector:target ratio required 8 weeks. We conclude that hyperprolactinemia decreases NK cell function. BrC corrects this by decreasing prolactin levels but also makes NK function more efficient by increasing the capacity of NK cells to recycle after killing.

Adult↗

PubMed1991

Immunohistochemical demonstration of androgen-binding protein in the rat prostatic gland.

Androgen-binding protein (ABP) is one of the best-characterized products of synthesis by the Sertoli cells in the rat. Although the exact physiological role of ABP remains to be determined, it has been widely used to study Sertoli cells and testicular function in this species. Since this protein is the principal carrier for testosterone in rat testis and epididymis, we decided to investigate ABP immunoreactivity (ABP-I) in androgen-dependent organs, including testicle, epididymides, prostate, and seminal vesicles. The location of ABP was investigated by immunohistochemistry using specific antisera against rat ABP. As previously described in the testis, rat ABP-I was identified in the seminiferous tubules within the cytoplasm of the Sertoli cells and the tubular luminae. The epididymis showed ABP-I only in epithelial cells of the proximal caput. We demonstrated ABP-I in the apical portions of epithelial cells of the rat prostate. Short-term castration and/or ligation of the efferent ducts did not suppress prostatic ABP-I. ABP-I was not present in seminal vesicles of control rats nor under any of the experimental conditions used throughout this study. The results also indicate the presence of ABP-I in prostatic epithelium, probably because of a mechanism similar to that described in epididymis. Our data support and enhance the concept that ABP may serve as a transmembrane carrier protein for androgens in androgen target organs in the male reproductive tract.

Androgen-Binding Protein↗

PubMed1990

Genetic polymorphism of the human sex hormone-binding globulin: evidence of an isoelectric focusing variant with normal androgen-binding affinities.

Human sex hormone-binding globulin (hSHBG) is a plasma glycoprotein composed of two identical subunits. The protein, which has high affinity for testosterone and estradiol has been purified to homogeneity. In this study we have investigated, on neuraminidase-treated serum samples, the presence of genetic variations of hSHBG by polyacrylamide gel isoelectric focusing (IEF). Based on IEF analyses of 110 serum samples from adult Mexican individuals we have identified two distinct IEF-patterns. The most frequent phenotype (95.45%) was characterized by two IEF-bands with pIs of 6.50 and 6.63, respectively. In five serum samples, a different 4-band pattern with pIs of 6.50, 6.63, 6.70 and 6.76 was identified. Family studies showed that this pattern was genetically determined. The frequency of this variant was 4.55%, and the observed phenotypes were consistent with the expression of an autosomal genetic system. The estimated gene frequencies for both alleles were shown to be in genetic equilibrium. Affinity constants, binding kinetics and serum concentrations of hSHBG from individuals having a 4-band pattern were similar to those obtained in individuals with a 2-band pattern, thus suggesting that the mechanism responsible for the generation of polymorphic variants of hSHBG reported herein did not involve the steroid binding site of the molecule. These findings may be of broad interest, as other serum binding proteins express genetic variants, which may permit their further structural and functional subclassification.

Adult↗

PubMed1989

Absorption of dihydrotestosterone (DHT) after its intramuscular administration.

In order to produce a sustained release system for natural androgens, two groups of six hypogonadal males received intramuscular (IM) 40 mg crystalline dihydrotestosterone (DHT), either with particle size of less than 50 microns (DHT-M) or between 100 and 150 microns (DHT-C). Serum DHT was analyzed through 51 days of follow-up. In the DHT-M group, serum DHT was above pretreatment values for 17 days, whereas in the DHT-C group, this period was extended over 50 days. The area under the serum concentration-time curve and the half-life of absorption calculated for the DHT-C group were greater than those obtained for the DHT-M group (55.1 ng/day/ml and 21 days vs. 14.5 ng/day/ml and 6 days; P less than 0.01). The authors conclude that DHT injection appears to be an effective and convenient technique for restoring serum physiologic DHT levels. This approach is suitable for long-term substitution therapy.

Absorption↗