Usefulness of early morning urine estrone-3-glucuronide assay in the monitoring ovarian secretory function in precocious puberty.

To evaluate the usefulness of the urinary estrone-3-glucuronide (EI-3-G) in the monitoring of the ovarian function in girls, we studied 11 girls with idiopathic central precocious puberty (ICPP) treated with LHRH analogs (LHRHa) for 2-5 years. Plasma LH, FSH, 17-beta-Estradiol (E2) levels, early morning urine (EMU) E1-3-G concentrations, were assessed before and 3, 6, 12 months after the onset of treatment. As expected, mean basal plasma LH, FSH and E2 concentrations, as well as mean basal EMU E1-3-G levels were significantly (p < 0.01) higher in patients studied than in normal, age matched, prepubertal controls. Three out of the 11 sexually advanced girls showed undetectable (< 15 pg/ml) basal plasma E2 values. On the contrary, in each patient studied, individual basal E1-3-G levels were higher than in normal age-matched prepubertal girls. LHRHa treatment significantly suppressed both basal and peak stimulated plasma gonadotropins, plasma E2 and EMU E1-3-G. However, while serum E2 levels were below the assay detection limit, not allowing to assess the degree of gonadal suppression, E1-3-G urinary concentrations were detectable in each subject treated, in the range of the normal prepubertal values. EMU E1-3-G determination seems to be a very sensitive and reliable approach to the monitoring of the effectiveness of LHRHa treatment in sexually advanced girls, allowing to detect very low estrogen concentrations and to achieve the desired ovarian suppression.

Precocious puberty: auxological criteria discriminating different forms.

It may be possible to recognize different forms of precocious puberty at the first evaluation. In a group of 26 sexually precocious girls we used Bayley-Pinneau predicted adult height (P.A.H.) to discriminate patients with 'poor' or 'good' height prognosis. Patients with evidence of impaired height prognosis (P.A.H. < -1 SDS) (Group 1) were immediately treated with LH-RH analogs, while patients with unimpaired height prognosis (P.A.H. > -1 SDS) (Group 2) were followed without therapy. Two yr of treatment significantly improved P.A.H. in Group 1 patients, from a mean of -1.68 +/- 0.4 to a mean of -0.57 +/- 0.6 (SDS) (p < 0.01). After the 2 yr observation period, Group 2 patients showed no significant variation of P.A.H. (from a mean of 0.45 +/- 0.8 to a mean of 0.33 +/- 0.6). The retrospective analysis of the growth pattern changes in the two Groups seems to indicate that LH-RH agonist treatment improves height potential in girls with initial poor height prognosis and that girls with initial good height prognosis maintain an unimpaired growth potential.

Natriuretic hormone receptors and actions on bone endothelial cells.

[125I]Atrial natriuretic peptide (ANP) was used to identify ANP receptors on a clonal line of bovine bone endothelial (BBE) cells. Specific binding of [125I]ANP was saturable and of high affinity. Computer analysis of the equilibrium binding data indicated that the Scatchard plots are best fit by a straight line (Kd = 69.3 +/- 20.9 pM; binding capacity = 37.9 fmol/10(6) cells). The order of potency for competing with [125I]ANP binding was human ANP (hANP) > rat atriopeptin-1 (rAP-1) > porcine brain natriuretic peptide (pBNP) > porcine C-type natriuretic peptide. Affinity cross-linking studies indicated the presence of two major 130- and 70-kilodalton bands that specifically bound to hANP, rAP-1, pBNP, and porcine C-type natriuretic peptide. The binding of natriuretic peptides to BBE cells resulted in an increase in cGMP production and a significant decrease in Na+/K+/Cl- cotransport, without effects on cAMP intracellular accumulation. hANP, rAP-1, and pBNP at 100-nM concentrations, significantly inhibited PTH-induced cAMP production. Treatment with natriuretic hormones was also associated with an increase in 6-keto-prostaglandin F1 alpha levels in the culture medium of BBE cells and a higher cell growth rate. These studies demonstrate that bone endothelial cells bear receptors for natriuretic hormones associated with changes in PTH-induced cAMP production, prostaglandin production, and cell proliferation.

Evidence for a storage pool defect in platelets from cirrhotic patients with defective aggregation.

The mechanisms underlying the defective platelet function in cirrhotic patients were investigated. Eleven cirrhotic patients with mild disease (group 1), 20 patients with severe cirrhosis (group 2), and 31 controls were studied. Platelet aggregation was significantly reduced in cirrhotics compared with controls. Compared with controls, cirrhotic patients in group 2 showed a significant reduction in the total content of adenosine triphosphate (57.8 +/- 7.8 vs. 26.1 +/- 6.3 mumol/10(11) platelets; P less than 0.05), 5-hydroxytryptamine (285 +/- 26 vs. 104 +/- 38 nmol/10(11) platelets; P less than 0.05), beta-thromboglobulin (2129 +/- 120 vs. 1223 +/- 161 ng/10(8) platelets; P less than 0.01), and platelet factor 4 (1389 +/- 108 vs. 805 +/- 176 ng/10(8) platelets; P less than 0.05). In patients with severe disease, an increase in plasma beta-thromboglobulin-platelet factor 4 ratio, an index of in vivo platelet activation, was observed (controls, 3.50 +/- 0.50; group 1, 4.02 +/- 0.80; and group 2, 6.59 +/- 1.15). Our data indicate the existence of a platelet storage pool defect, which may favor the bleeding tendency of cirrhotic patients.

Natriuretic peptide receptors regulate endothelin synthesis and release from parathyroid cells.

Cloned rat parathyroid cells (PTr cell line) that produce parathyroid hormone-related peptide plus endothelin 1 and primary cultures of human parathyroid cells were tested for growth and differentiation responses to atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). High- and low-affinity binding sites for ANP were found on PTr cells; BNP appeared to bind to the same receptors with similar affinities. Either ANP or BNP stimulated production of cGMP and caused a 30% decrease in Na(+)-K(+)-Cl- cotransport. Each peptide increased synthesis and secretion of endothelin 1 by PTr cells in a dose-dependent fashion, but cell growth was not affected. Human parathyroid cells (normal and pathological) also responded to ANP or BNP with an increase in cGMP production. The finding of receptors for natriuretic hormones on parathyroid cells with consequent effects on release of endothelin 1 might be of relevance in understanding the clinical association between hyperparathyroidism and hypertension.