Plasma steroid transport in subjects with tumors of hormonal target organs: a review.

Tumors derived from a hormonal target organ are assumed to be stimulated by the same hormone that stimulates the normal target tissue. In spite of attempts to acquire direct indications of a correlation between hormones and cancer, none have been definitive because studies of total and free hormone levels have given contradictory results. For this reason, attention has shifted to the study of plasma binding and transport of hormones, that is, of the proteins responsible for modulation of the hormone effect and thus of hormone bioavailability. The data reviewed indicate that in-depth study of the transport and binding system of sex steroids would give new information about the endocrine characteristics of cancer patients.

Breast carcinoma and skeletal formation.

We have studied skeletal structure in 67 women with breast carcinoma and in 59 women without breast carcinoma, looking for differences of development that might be correlated with hormonal, metabolic or genetic abnormalities. We have measured the lengths of the limbs and of their segments (upper arm, forearm, thigh, leg), of the bisacromial and bitrochanteric transverse diameters and total height and height divided into the parts from vertex to pubis and from pubis to the ground. The analysis showed statistically significant coefficients of regression with presence of mammary carcinoma for height (0.0904262, S.D. 0.0461), length of thigh (0.12989, S.D. 0.03981) and length of lower leg (-0.68475, S.D. 0.1390). This skeletal type might be the expression of a genetic condition that is associated with the existence of mechanisms that permit development of mammary cancer.

[Prospectives of the study of seminal fluid in the diagnosis of infertility]. / Prospettive di studio del plasma seminale nella diagnostica dell'infertilità.

Biochemical components usually evaluated in seminal plasma are lower than those in blood serum. In this study the concentration of different constituents in seminal plasma has been analyzed: creatinine, urea, glucose, uric acid, sodium, potassium, triglycerides, cholesterol, bilirubin, alkaline phosphatase, glutamic oxalacetic transaminase (SGOT), glutamic pyruvate transaminase (SGPT), cholinesterase, creatin phospho chinase (CPK), gamma glutamyl transpeptidase, lactic dehydrogenase (LDH), proteins, in comparison with the concentrations of the same constituents in blood. With the exception of uric acid, all the biochemical components in the seminal plasma were either significantly higher or lower than in blood serum, an index of the complexity of the mechanism regulating the presence and distribution of the single components in seminal plasma compared with blood serum. Isoelectro-focussing for proteins showed, in seminal plasma, a higher quantity of fragments and a different distribution of this in comparison with blood serum.

Plasma sex hormone binding globulin in patients with prostatic carcinoma.

The concentrations of sex hormone binding globulin (SHBG) were measured in the plasma of 56 men, who were 47 to 85 years of age, by time-resolved immunofluorometric assay with a monoclonal antibody. Twenty-five of the men had untreated carcinoma of the prostate and 17 had untreated prostatic hyperplasia. There were 14 healthy control subjects. SHBG levels were significantly higher in patients with prostatic carcinoma (37.6 +/- 8.4 nmol/l) than in those with prostatic hyperplasia (24.5 +/- 5.2 nmol/l; P less than 0.05) or control subjects (14.9 +/- 2.8 nmol/l; P less than 0.01). It is not known why SHBG levels are higher in patients with carcinoma or hyperplasia of the prostate. The contradictory results obtained in other studies may be due to heterogeneity of the binding globulin causing its values to vary in the different assays used.

Breast carcinoma and plasma 17-beta-estradiol binding.

The data relating to plasma steroid binding and transport (usually measured with dehydrotestosterone) are controversial. The plasma E2 binding of 79 breast carcinoma patients, 19 premenopausal and 60 postmenopausal, were compared to 46 controls, 21 premenopausal and 25 postmenopausal. In this study the authors removed the endogenous steroids with charcoal, incubated the plasma with 17-beta-E2 in non-saturation conditions, and used ammonium sulfate to precipitate the complex. The authors chose 17-beta-E2 as ligand because the plasma steroid binding system has not been shown to be homogeneous and because this binding function may vary independently for the different steroids. In these patients, the E2 binding was significantly (P less than 0.01) increased (85 +/- 11 pg/ml and 73 +/- 13 pg/ml in premenopausal and postmenopausal) compared to the normal controls (59 +/- 7 pg/ml and 58 +/- 5 pg/ml in premenopausal and postmenopausal women. It is still unclear whether this is a primary increase of the binding capacity or a reaction of the host for sequestering excess circulating E2. However, the small percentage of false-positives and false-negatives suggests that E2 binding could be used as a tumor marker in breast carcinoma.

Current status of hormone receptor measurements in cancer patients.

Despite increasingly sophisticated techniques, improvements in the correlation between laboratory findings and tumor response to endocrine therapy have not been obtained by hormone receptor studies. A possible explanation is that present knowledge of the mechanisms of the endocrine stimulus is incomplete. Some aspects of the present model, (elevated conjugated steroid levels, multiplicity of the plasma proteins capable of binding hormones, pulsatility of the plasma protein bond and of the receptor system for steroids), are still unclear and thus are not used in diagnosis. By evaluating these factors it will probably be possible to correlate better laboratory data with clinical findings.

Development of laboratory hormone tests and their application in the monitoring of cancer patients.

In the endocrinologic study of dysplastic and neoplastic pathologies of hormone-dependent organs we propose the determination not only of the plasma levels of the "total" hormone but also those of the free hormone as well as the plasma/hormone binding capacity and the kinetics of the plasma/steroid interaction.

Patterns of transport and binding of sex steroids.

The seminal plasma-sex steroid binding kinetic was evaluated by measuring the amount of labeled hormone extractable after 5 sec to 100 min of incubation. For testosterone in normal subjects, a peak of binding was reached after 30 sec of incubation. In subjects with severe oligoasthenospermia the kinetic pattern for testosterone was different but similar to the binding kinetic between seminal plasma of normal men and estradiol. The phenomena did not occur with frozen plasma samples.