Binding of [3H]arginine vasopressin (AVP) and [3H]oxytocin to primary monolayer cultures of bovine adrenal chromaffin cells was time-dependent, and the binding sites for each peptide were specific and saturable. Studies with the V1 AVP antagonist d(CH2)5Tyr(Me)2-AVP, the V2 agonist 1-deamino-8-D-AVP and the V2 antagonist d(CH2)5D-Leu2,Val4-AVP indicated that the AVP receptor was V1 in specificity. Scatchard plots showed that each ligand interacted with a single high-affinity, low-capacity binding site: oxytocin dissociation constant (Kd) 0.29 +/- 0.02 nmol/l, maximum binding capacity (Bmax) 7.6 +/- 0.2 fmol/10(6) cells (or 4500 +/- 102 sites/cell) (n = 3); AVP Kd 0.09 +/- 0.02 nmol/l, Bmax 5.1 +/- 0.63 fmol/10(6) cells (or 3050 +/- 318 sites/cell) (n = 3). Although forskolin in concentrations from 1 nmol/l to 1 mmol/l stimulated cyclic AMP (cAMP) production in isolated chromaffin cells, this did not result in detectable catecholamine release. Neither AVP nor oxytocin in concentrations between 10 pmol/l and 10 mumols/l stimulated cAMP production in these cells. Vasopressin in concentrations as low as 10 pmol/l stimulated a sixfold increase in total inositol phosphates; the dose-response curve was triphasic. Oxytocin had little effect on total inositol phosphate accumulation at low concentrations, but concentrations above micromolar stimulated total inositol phosphate production approximately fourfold. There was no measurable release of catecholamines in response to either peptide. The physiological consequences of these AVP-induced changes in inositol phosphate concentrations remain to be elucidated.

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Bone mineral density (BMD) was evaluated by dual energy x ray absorptiometry in 60 adults (33 males, 27 females; aged 50, range 23-76 years) who were growth hormone deficient from various causes for 10-4 (1-31) years. Adult patients who had acquired growth hormone deficiency before completion of puberty had significantly reduced mean (SEM) BMD compared with age matched healthy controls at the lumbar spine: 0-87 (0.09) v 1-20 (0.03) g/cm2, femoral neck: 0-81 (0-06) v 1-08 (0.04) g/cm2, and Ward's triangle: 0-68 (0.07) v 1-04 (0.05) g/cm2. These values were also reduced compared with those of patients who had received human growth hormone during puberty. Untreated growth hormone deficiency when present during puberty results in reduced adult bone density.

Having noted symptomatic osteoporotic vertebral collapse in young adult survivors of childhood malignancy, bone mineral density (BMD) was examined at three sites by dual‐energy X‐ray absorptiometry in 64 patients treated in childhood for intracranial malignancy (group 1; n = 21) or acute leukaemia (group 2; n = 43). Patients in group 1 were selected for growth hormone deficiency (GHD) by auxological and biochemical criteria before the end of puberty (Tanner stage V). Seven patients (six men; mean (± SEM) age at study, 28.0 ± 2.9 years; mean age at diagnosis, 8.7 ± 1.5 years) in this group had been treated with human pituitary growth hormone (GH) for 1–12 years; and 14 patients (nine men; mean age at study, 26.8 ± 1.0 years; mean age at diagnosis, 10.7 ± 1.4 years) had not received GH. Bone densities in group 1 were normal in the GH‐treated patients at the femoral neck (98.4 ± 3.8% of control), lumbar spine (100.4 ± 6.1% of control) and Ward's triangle (101.0 ± 6.1% of control) but markedly reduced in the untreated group (femoral neck, 81.2 ± 2.6% of control (p= 0.002); lumbar spine, 79.1 ± 4.1% of control (p= 0.04); Ward's triangle, 80.1 ± 3.6% of control (p= 0.01)). The majority of patients in group 2 had been treated for acute lymphoblastic leukaemia (ALL) and were in three subgroups. Fifteen (ten men; mean age at study, 22.1 ± 0.8 years; mean age at diagnosis, 5.7 ± 0.8 years) had no auxological evidence of GHD, ten (six men; mean age at study, 18.8 ± 0.7 years; mean age at diagnosis, 6.6 ± 1.2 years) received GH therapy for a mean of 2.6 years (range, 0.5–5.0 years), while 14 patients (three men; mean age at study, 20.9 ± 0.4 years; mean age at diagnosis, 5.1 ± 0.8 years) had GHD but did not receive GH. A small group of four patients (three men; mean age at study, 23.2 ± 2.1 years; mean age at diagnosis, 8.0 ± 2.3 years) who had been treated for acute myeloid leukaemia (AML) in childhood was also studied. The patients with AML had normal bone densities at all three sites (femoral neck, 106 ± 6.1% of control; lumbar spine, 96.5 ± 3.0% of control; Ward's triangle, 110.8 ± 9.3% of control), as did the patients with ALL who did not have GHD (femoral neck, 102.3 ± 2.9% of control; lumbar spine, 98.6 ± 1.7% of control; Ward's triangle, 108.3 ± 3.2% of control). The patients with ALL and GHD not treated with GH had markedly reduced BMD at all three sites (femoral neck, 90.5 ± 2.6% of control; lumbar spine, 88.4 ± 2.5% of control; Ward's triangle, 94.5 ± 3.7% of control), but those treated with GH had a BMD no different from control (femoral neck, 100.6 ± 3.3% of control; lumbar spine, 95.7 ± 4.6% of control; Ward's triangle, 106.2 ± 4.9% of control). It is concluded that GHD during childhood and adolescence predisposes to osteopenia.

OBJECTIVE: To investigate whether osteoporosis occurs after surgical treatment for obesity. DESIGN: A cross-sectional study of ®ve groups of subjects who had undergone surgical treatment for obesity: ®ve premenopausal women; 13 post-menopausal women; seven post-menopausal women taking oestrogen replacement (HRT); ®ve men; and six women who had undergone surgical reversal (mean time 7 y). SUBJECTS: Thirty-six Caucasian subjects who had undergone jejunoileal or pancreaticobiliary bypass surgery at St George's Hospital between 1971 and 1992. Their mean age was 50.8 y (range 32 ± 69 y) and the median time since the operation was 14.8 y (range 4 ± 23 y). MEASUREMENTS: A clinical questionnaire was used to exclude possible factors, which might in¯uence bone mineral density. A single blood sample was collected for measurement of calcium, phosphate, alkaline phosphatase, albumin, magnesium, zinc, creatinine, thyroxine, 25-hydroxy-vitamin D, sex steroids, gonadotrophins and IGF-1 and 24 h urine calcium excretion was measured. Bone mineral density (BMD) was measured in the lumbar (L2-L4) spine (LS) and femoral neck (FN) by dual energy X-ray absorptiometry (DEXA). RESULTS: There was no difference in serum calcium, alkaline phosphatase, IGF-1, 25-hydroxy-vitamin D (25-OH vitamin D), magnesium or zinc concentrations between the ®ve groups. The LS-BMD T score was lower (P`0.05) in male subjects ( 7 2.08 AE 1.04 mean 1.0 AE s.d) and post-menopausal women not taking HRT ( 7 1.21 AE 1.33) compared to the surgically reversed group (0.87 AE 2.36). The male group was most severely affected, despite normal serum testosterone concentrations. Two of the ®ve men studied, had a LS-BMD T score`7 2.5 and two had a LS-BMD T score between 7 1.0 and 7 2.5. In contrast, six of the seven post-menopausal women on HRT had an LS BMD T score b 7 1.0. There was no difference in the FN-BMD between the ®ve groups. The presence of low BMD was not related to age, duration of bypass, or degree of postoperative weight loss. Iliac crest bone biopsies in three subjects with low BMD, con®rmed the presence of osteoporosis. CONCLUSIONS: Reduced bone mineral density is a complication of jejunoileal bypass surgery.