N. Fröhlander

Haptoglobin Groups in Ovarian Carcinoma

Haptoglobin groups were determined in 182 patients with primary ovarian carcinoma. Previously reported associations could not be confirmed. A significant excess of HP2-1 was observed among patients with a family history of cancer.

Growth hormone and somatomedin C during post- menopausal replacement therapy with oestrogen alone and in combination with an antioestrogen

Serum concentrations of growth hormone (GH) and somatomedin C were monitored in 14 women during post-menopausal replacement therapy with oestrogen alone and in combination with a specific antioestrogen. During 3 mth of treatment with ethinyl oestradiol (10 micrograms daily), the mean serum GH level rose from 2.8 +/- 0.78 mU/l (mean +/- S.E.M.) to 6.5 +/- 0.39 mU/l, whereas the concentration of somatomedin C fell from 22.4 +/- 0.89 to 15.4 +/- 0.43 nM. These changes during unopposed oestrogen treatment were clearly reversed by the addition of tamoxifen (20 mg daily), following which GH concentrations fell to pre-treatment levels. It is suggested that oestrogens inhibit somatomedin C production in the liver and that GH secretion may play an important role in regard to certain liver effects induced by oral oestrogen therapy.

Haptoglobin groups and rheumatoid arthritis.

Haptoglobin types were determined in 200 patients with rheumatoid arthritis (RA) subdivided according to sex and familial occurrence of polyarthritis. A highly significant excess of the Hp2 gene was found among patients with a family history of polyarthritis, more pronounced among males. The possible association between Hp2 and predisposition for increased immune reactivity is discussed.

Haptoglobin Groups and Lung Cancer

Haptoglobin groups were investigated in 309 patients with primary lung cancer divided by sex, smoking habits and tumor type. Patients with squamous epithelial cancer and oat-cell cancer showed no significant difference from normal controls. Among patients with pulmonary adenocarcinoma the frequency of the Hp 2-2 type was significantly (p less than 0.05) lower compared to the controls, with a corresponding increase of the Hp 1-1 and Hp 2-1 types. This difference was more pronounced (p less than 0.025) among females with pulmonary adenocarcinoma.

Haptoglobin synergistically potentiates bradykinin and thrombin induced prostaglandin biosynthesis in isolated osteroblasts

Haptoglobin of two different phenotypes (Hp 1-1 and Hp 2-1) dose-dependently (1-4 mg/ml) stimulated the formation of prostaglandin E2 (PGE2) in osteoblast-like cells isolated from neonatal mouse calvarial bones. The degree of stimulation obtained by haptoglobins (4 mg/ml) on PGE2 biosynthesis was in the same range as that caused by bradykinin (1 mumol/l). Pretreatment of osteoblasts with Hp 1-1 or Hp 2-1 (1-4 mg/ml) resulted in a dose-dependent, synergistic potentiation of the stimulatory effect of bradykinin (1 mumol/l) on PGE2 formation. Thrombin (7 U/ml) stimulated PGE2 formation in the osteoblast-like cells by a mechanism that was also synergistically potentiated by haptoglobin (2 mg/ml). These data show that haptoglobin per se stimulates PGE2 biosynthesis in isolated osteoblasts and, in addition, synergistically potentiates the effect of bradykinin and thrombin. Consequently, the enhanced production of haptoglobin seen in different inflammatory processes may contribute to the destruction of bone by inducing the formation of prostanoids capable of stimulating bone resorption.

Association between Haptoglobin Groups and Hereditary Predisposition for Bronchial Asthma

Haptoglobin (Hp) groups were investigated in 148 patients with bronchial asthma. A significant (p less than 0.005) deviation from the expected Hardy-Weinberg equilibrium, with a decreased frequency of heterozygotes, was observed among patients with a family history of asthma. This deviation was more pronounced among patients with adult onset of asthma. The presence or absence of atopy had no significant influence on the phenotype distribution.

Haptoglobin Groups in Acute Myocardial Infarction

In patients with acute myocardial infarction, the haptoglobin (HP) groups were found to be associated with serum cholesterol levels. Heterozygotes (HP 2-1) showed serum cholesterol levels significantly higher (p less than 0.0001) than those of patients with HP 1-1 or HP 2-2. Furthermore, an association between HP type and infarction size was observed, HP 2-2 being associated with smaller infarctions.

Continuous 24-hour secretion of growth hormone during late pregnancy: a regulator of maternal metabolic adjustment?

A dramatic change in growth hormone secretion was demonstrated during the 3rd trimester of human pregnancy, when compared with the non‐pregnant state. The pulsatile pattern, with intermittent high peaks, and low or undetectable levels between peaks, characteristic of normal men and non‐pregnant women, was completely abolished. All the 10 pregnant women investigated had the same stable basal circulating growth hormone concentration. Values were in the range 6–10 mu/l and there was no evidence of pulsatile activity. Previously, in animal experiments, a continuous secretion of growth hormone has been shown to ‘feminize’ hepatic steroid metabolism, hepatic prolactin receptors, hepatic sulphatase activity and to stimulate pregnancy protein synthesis. The same biological principle could be valid also during human pregnancy and be related to maternal metabolic adjustment.

Association between haptoglobin groups and aortic abdominal aneurysms.

Six different serum group systems (Bf, C3, Gc, Hp, Pi and Tf) were studied in a series of patients from northern Sweden with abdominal aortic aneurysms. In the haptoglobin system an increased frequency of the Hp 2-1 type was observed among the patients. No association was found between abdominal aortic aneurysms and the other five serum group systems.

Heterozygosity Effects in Studies of Genetic Markers and Disease

Examples were discussed where heterozygosity was associated with increased or decreased disease risks and where the apparent mechanism is direct functional involvement of gene products and not linkage disequilibrium. Special attention was paid to the impact of Hp (haptoglobin) heterozygosity on a number of different multifactorial disorders. When phenotype distributions in patients show large deviations from the Hardy-Weinberg equilibrium significant differences between patients and controls may be found concerning phenotype distributions but not with respect to the frequencies of alleles and phenotypic factors. The common method of studying ratios of phenotypic factors by pooling homo- and heterozygotes is in principle a conservative approach which tends to underestimate the strength of associations and to obscure heterozygosity effects. A significant deviation from the Hardy-Weinberg equilibrium in a marker system examined in a group of patients is in itself a sensitive indicator of phenotypic association with the disease in question.