[Albright's osteodystrophy with secondary hyperparathyroidism].
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Adult↗
Biomedical subjects
M Pugeat
Publications and source records attributed to M Pugeat.
Influence of glycosylation on the clearance of recombinant human sex hormone-binding globulin from rabbit blood.
Human sex hormone-binding globulin (hSHBG) is a plasma glycoprotein that binds sex steroids with high affinity. Variations in hSHBG glycosylation contribute to its electrophoretic microheterogeneity, but the functional significance of different SHBG glycoforms is unknown. Carbohydrates may influence the biological activities and half-lives of glycoproteins and we have examined how oligosaccharides at specific sites influence the plasma clearance of hSHBG in vivo. To accomplish this, fully-glycosylated hSHBG, or hSHBG mutants lacking specific oligosaccharides chains, were expressed in Chinese hamster ovary (CHO) cells and purified by immunoaffinity chromatography. The purified recombinant proteins were then biotinylated to study their plasma half-lives after intravenous injection into rabbits. When compared to hSHBG isolated from serum, recombinant hSHBG migrates with a slightly larger average molecular size during denaturing polyacrylamide gel electrophoresis. This is due to a greater proportion (33-39% vs. 3%) of more highly branched N-linked oligosaccharides on the recombinant proteins. When injected into rabbits, the disappearance of recombinant hSHBG showed two exponential components, as previously shown for natural hSHBG in the same animal model. The mean +/- S.E.M. plasma half-lives of recombinant hSHBG (t 1/2alpha 0.11+/-0.03 h and t 1/2beta 18.94+/-1.65 h) are shorter than previously measured for natural hSHBG (t 1/2alpha 3.43+/-0.72 h and t 1/2beta 38.18+/-7.22 h) and this is likely due to differences in the composition of their N-linked oligosaccharides. An O-linked chain at Thr7 does not influence the plasma clearance of hSHBG in the presence or absence of N-linked carbohydrates at Asn351 and Asn367. However, a 1.5-1.6 fold (p<0.03) increase in plasma half-life of variants lacking both N-glycosylation sites was observed and this is probably due to the fact these variants are not recognized by the asialoglycoprotein receptor-mediated clearance system. Removal of either N-glycosylation consensus site also increased (p<0.0001) the plasma half-life of hSHBG by 2.3 2.4 fold. Thus, the metabolic clearance of hSHBG appears to be determined by the number of N-linked oligosaccharides rather than their location.
Animals↗
[Genetics of the polycystic ovarian syndrome and therapeutic perspectives ].
PCOS is the most frequent endocrine disorder of premenopausal women. The common clinical signs of PCOS are hirsutism, menstrual irregularities with chronic anovulation and a trend toward overweight or obesity. Diagnosis is based upon high plasma levels of androgens and the ultrasound image of polycystic ovaries. The high prevalence of PCOS at first degree female relatives suggest an important genetic component of this syndrome. Linking studies in sisters presenting phenotypical traits of PCOS and in their parents allowed the investigation of certain candidate genes presumed to be involved in the physiopathology of PCOS. The genes encoding enzymes involved in androgen synthesis, protein transducers of insulin signals and the paracrine regulating factors of gonadotrophins and ovarian function have been analysed. To date, no determinant gene mutation was reported. However, several loci were detected, especially a locus within the insulin receptor. Mutations or gene polymorphisms and their function remain to be identified. These research attempts should explain the physiopathology of PCOS and open new therapeutic perspectives. The usage of medication increasing the sensitivity to insulin action is an example of applying these particular aspects.
Androgens↗
[Hepatocellular carcinoma and hyperestrogenia in a male].
The case of a 38 year-old man with hepatocellular carcinoma in a non-cirrhotic liver is reported. Hyperestrogenosis with gynecomastia, polycythemia and proteinuria were present. After complete removal of the tumor, estrogen levels, red blood-cell volume and urine analysis did not return to normal and these pathologic findings were probably not paraneoplastic syndromes. Outcome was good, the patient remaining completely well without evidence of recurrence during the ensuing 30 months. The likely explanation for the persistent hyperestrogenosis was an excessive conversion of sexual hormones. The authors suggest that this abnormal hyperestrogenic state could promote hepatic neoplasia as it has been established in animals.
Adult↗
[Luteal insufficiency and elevation of sex-binding proteins by demegestone].
Demegestone, a norprogesterone derivative, was administered during the luteal phase in 6 normally ovulatory women and in 10 patients with luteal insufficiency. Demegestone decreased the LH surge and the plasma concentrations of estradiol and progesterone in the normally ovulatory women and did not modify the binding capacity of sex steroid binding protein (SBP). In the patients with luteal insufficiency, demegestone increased significantly SBP (0.94 +/- 0.24 vs 1.32 +/- 0.56 micrograms/dl, p less than 0.05) and decreased the free testosterone index (T/SBP) (38.8 +/- 33.3 vs 25.4 +/- 18.5, p less than 0.05). Transcortin, was unchanged during demegestone treatment in both groups of women. The results showed that demegestone did not exercise androgenic activity on SBP conversely to the nortestosterone derivatives which decrease SBP and confirmed that progesterone and norprogesterone derivatives influence positively the regulation of SBP.
Adult↗
[Serum testosterone after HCG in thyroidectomized or hyperthyroid male rats (author's transl)].
Serum testosterone levels were measured by radioimmunoassay in young male rats before and after IM HCG (500 IU) in basal conditions, after thyroidectomy, or during thyroxine administration. Basal testosterone levels decreased significantly with time in control group (p less than 0.025) and in thyroidectomized rats (p less than 0.025). After HCG, testosterone increased in the 3 groups. There was no difference between control and hypothyroid groups but a lower response (p less than 0.005) in hyperthyroid rats.
Animals↗
[Adrenocortical carcinoma with feminization: "in vivo" and "in vitro" study (author's transl)].
A 31 year-old man with adrenocortical carcinoma is presented. Clinically he had a recidiving gynecomastia. The levels ddhydro-épi-androstérone (D.H.E.A.) and his ester Sulfate (D.H.E.A.S.), delta-4-androsténédione (A), estrone (Et), estradiol (E2) in urines, serum and tumor were very high. The cortisol production rate was in normal values. The serum levels or cortisol, D.H.E.A., D.H.E.A.S. and A were not increased by A.C.T.H. injection. In vitro, steroidogenesis in the tumor cells was not influenced by A.C.T.H. or prostaglandin E1, but stimulated by dibutyryl cyclic 3'5' adenosine monophosphate. Unresponsiveness of A.C.T.H. was related to an alteration of cells membranes receptors.
Adrenal Cortex Neoplasms↗
[Hyperandrogenism in hirsute and obese women. Effects of a low calorie diet].
To investigate the relationship between overweight and hyperandrogenism, a 1500 kcal/day diet was prescribed for 4 months to 23 hirsute and obese patients. This diet decreased body mass index from 29.9 +/- 4.9 to 27.2 +/- 4.4 kg/m2 (P < 0.008), but had no significant effect on fasting insulin levels (18.9 +/- 14.2 vs. 21.1 +/- 9.6 mlU/l). Weight lost increased significantly (P < 0.008) the plasma concentration of sex-hormone binding-globulin (SHBG) from 21.2 +/- 10.6 to 26.2 +/- 13.5 nmol/l and decreased significantly (P < 0.04) the SHBG-unbound testosterone concentration from 9.3 +/- 6.2 to 7.2 +/- 4.8 ng/dl, without changing the concentrations of the main androgens measured in this study. Moreover, during diet 5 patients in amenorrhea and 8 among 13 patients with irregular menstrual cycle recovered regular menses. We concluded that the control of excess body weight in hirsute women is effective but not sufficient to improve hyperandrogenism.
Adolescent↗