Effect of Administration of a Combined Estrogen-Progestin Contraceptive on the Level of Individual Plasma Proteins

Cb, Laurell; Kullander, Stig; Thorell, Jan I.

doi:10.3109/00365516809077003

Cited by 180 publications

(42 citation statements)

References 30 publications

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“…Although it is important to integrate these adverse effects with a consideration of the risks and benefit of chronic danazol administration to al-antitrypsin deficient patients, danazol is the first example of an agent that offers practical therapeutic potential to these individuals. Previous studies have shown that the administration of combination estrogen-progestin oral contraceptives increases serum al-antitrypsin levels in normal individuals and those with intermediate serum deficiency of al-antitrypsin, but produces no effect in the PiZ individual (37). Similar results are reported for diethylstilbesterol administration (13).…”

Section: Resultssupporting

confidence: 78%

Danazol-induced Augmentation of Serum α1-Antitrypsin Levels in Individuals with Marked Deficiency of this Antiprotease

Gadek¹,

Fulmer²,

Gelfand³

et al. 1980

J. Clin. Invest.

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A B S T R A C T Individuals with serum al-antitrypsin levels below 80 mgldl are clearly at risk for the development of accelerated panacinar emphysema. One possible approach to the therapy of this disorder would be to raise serum levels of this major antiprotease to establish protease-antiprotease homeostasis within the lung parenchyma. Because danazol, an impeded androgen, elevates levels of Cl inhibitor in patients deficient of that serum antiprotease, we hypothesized that this agent might also increase acl-antitrypsin levels in patients with al-antitrypsin deficiency. To evaluate this concept, seven patients with severe emphysema associated with al-antitrypsin deficiency (six PiZ and 1 MDUarteZ) and one asymptomatic individual (PiSZ) received 600 mg of danazol daily for 30 d. Five of the six PiZ patients responded to danazol therapy with significant increases in serum al-antitrypsin levels (mean increase of 37%; P < 0.03). The two individuals who were heterozygous for the Z protein increased their serum levels by 85% (PiMDuar,eZ) and 87% (PiSZ), respectively. These increases in serum al-antitrypsin antigen were accompanied by commensurate increases in serum trypsin inhibition. Crossed immunoelectrophoresis showed no alterations of the microheterogeneity of the al-antitrypsin or the presence of protease-antiprotease complexes in serum during danazol therapy. These data demonstrate that serum al-antitrypsin levels can be augmented by danazol therapy in PiZ individuals as well as those heterozygotes with

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Section: Resultssupporting

confidence: 78%

Danazol-induced Augmentation of Serum α1-Antitrypsin Levels in Individuals with Marked Deficiency of this Antiprotease

Gadek¹,

Fulmer²,

Gelfand³

et al. 1980

J. Clin. Invest.

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“…It would be of interest to assess serum levels of these two proteins in other types of illnesses. However, although inconclusive, it is noteworthy that in our parallel study, alpha2 HS and alpha, AT serum levels of a wooman taking oral contraceptives (34) were greatlv increased in parallel. These facts suggest that, because serum levels appear to be opposite, different stimuli could also produce different hepatic responses.…”

Section: Resultsmentioning

confidence: 93%

Serum concentration of human alpha 2 HS glycoprotein during the inflammatory process: evidence that alpha 2 HS glycoprotein is a negative acute-phase reactant.

Lebreton¹,

Joisel²,

Raoult³

et al. 1979

J. Clin. Invest.

327

176

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A B S T R A C T A nonspecific opsonin function has been ascribed to human alpha2 HS glycoprotein. Its serum level has been shown to be decreased in trauma patients. Recent studies from this laboratory revealed a heterogeneity among the final products obtained in the course of the preparation of the protein. To date, no definitive agreement existed with regard to a molecular homogeneous entity of alpha2 HS glycoprotein (Ba-alpha2 glycoproteins). The purpose of the current work was to study the variations in serum level ofalpha2 HS in patients suffering from an acute inflammatory process of bacterial etiology and to determine whether a decrease in alpha2 HS was accompanied by the appearance of fragments of this protein in the serum. A method of preparing alpha2 HS was thus developed, using an immune adsorbent as a final purification step. In an intermediary step of the preparation, alpha2 HS was found to bind zinc ions when metal chelate affinity chromatography was employed. Immunologically and physico-chemically pure alpha2 HS was obtained. The protein consists of a unique polypeptide chain of about 50,000 daltons and has a unique amino-terminal residue, alanine. However, the protein maintained its molecular integrity with difficulty, and spontaneous fragments ranging from 30,000 to <10,000 daltons were produced in some of the preparations. No major modification in the molecular structure of the protein was This work was presented in part at the Satellite Symposium "Current Concepts in Kinin Research" of the 17th International Congress of Pharmacology, Paris, July 1978.Received for publication 30 June 1978 and in revised form 16 April 1979. 1118 noted in the sera of subjects suffering from an acute inflammatory process. Serum level of alpha2 HS and alpha, antitrypsin (AT) was determined in 23 patients.When the acute-phase (AP-)reactant alpha, AT was increased (difference with normal mean >+2 or +3 SD), the sera showed a large decrease in alpha2 HS (difference with normal mean <-2 or -3 SD). The serum level of alpha2 HS, albumin, alpha2 macroglobulin, and of positive AP-reactants, orosomucoid, alpha, AT, haptoglobin, and ceruloplasmin was evaluated in a longitudinal study of seven patients. The results were submitted to a principal components analysis. Alpha2 HS showed a negative correlation with the AP-reactants alpha, AT, orosomucoid, and haptoglobin (P < 0.05) and a positive correlation with albumin (P < 0.05); these findings indicate that alpha2 HS is a negative AP-reactant. In addition, analysis of the principal components confirms the strong analogy between alpha2 HS and albumin and indicates that serum level behavior of the AP-reactants during the course of the disease closely depends on the protein studied.

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“…Pregnancy caused a significant rise in serum d|-antitryp sin [10,12], possibly the result of elevated protein ana bolism and/or tissue damage surrounding parturition [ 13] or as a response to glucocorticoid [11] or estrogen [13] stimulation. A rise in serum di-antitrypsin similar to that seen in pregnancy was demonstrated after admin istration of estrogen [14] or a combined estrogen/progestin contraceptive [15]. Studies of normal males receiving testosterone demonstrated a small but significant de crease in serum trypsin inhibitor [16], Other subsequent studies of several anabolic steroids demonstrated a vari able response of d r antitrypsin [17].…”

Section: Discussionmentioning

confidence: 81%

Response of Serine Antiproteases to Growth Hormone Therapy in Growth Hormone Deficient Children

et al. 1989

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Growth hormone regulates the hepatic mRNA levels of α₁-antitrypsin and two contrapsin-like mRNAs in the rat. To determine whether growth hormone regulates similar serine protease inhibitors in humans, we measured serum α₁-antitrypsin, α₁-antichymotrypsin, and antithrombin III by radioimmunodiffusion in 16 growth hormone deficient children before and after growth hormone therapy. Of the 19 determinations made, 17/19 showed an increase in α₁-antirypsin after administration of growth hormone, 198.6 ± 39.1 mg/dl before growth hormone and 239.4 ± 44 mg/dl after growth hormone (p = 0.005). Specificity of the response for α₁-antitrypsin was indicated by the fact that neither α₁-antichymotrypsin or antithrombin III values changed after growth hormone (p = 0.6 and 0.5, respectively). These data are compatible with the hypothesis that growth hormone regulates serine protease inhibitors in humans and suggests that investigation of other members of the serpin gene family might prove fruitful in defining additional growth hormone target genes.

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Effect of Administration of a Combined Estrogen-Progestin Contraceptive on the Level of Individual Plasma Proteins

Cited by 180 publications

References 30 publications

Danazol-induced Augmentation of Serum α1-Antitrypsin Levels in Individuals with Marked Deficiency of this Antiprotease

Danazol-induced Augmentation of Serum α1-Antitrypsin Levels in Individuals with Marked Deficiency of this Antiprotease

Serum concentration of human alpha 2 HS glycoprotein during the inflammatory process: evidence that alpha 2 HS glycoprotein is a negative acute-phase reactant.

Response of Serine Antiproteases to Growth Hormone Therapy in Growth Hormone Deficient Children

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