Expression of Somatostatin Receptor SST4 in Human Placenta and Absence of Octreotide Effect on Human Placental Growth Hormone Concentration during Pregnancy1

Abstract

In pregnancy, the human placenta GH acts as a growth-promoting hormone and appears to be the main stimulator of insulin-like growth factor I (IGF-I) secretion. In a woman with a TSH-secreting macroadenoma, successful treatment with the somatostatin analog octreotide was conducted during the first month and the second half of pregnancy without side-effects on placental and fetal development. As observed in normal pregnancy, both serum placental GH and IGF-I levels increased throughout pregnancy and dropped sharply after delivery. In placental membranes from both treated and healthy untreated patients, we demonstrated the presence of high affinity binding sites for somatostatin-14 (Kd, 4.6 and 5.3 nmol/L; binding capacity, 1.53 and 1.35 pmol/mg protein, respectively). These receptors displayed low affinity for octreotide (IC50, 1.2–2 μmol/L), suggesting the presence of SST1 and/or SST4 receptors. We found that messenger ribonucleic acids of these two subtypes were expressed in both human placental tissue and purified human cytotrophoblast cells. Finally, the SST1-selective analog, des-AA1,2,5[d-Trp8,IAmp9]S-14 had low affinity for placental somatostatin receptors. These results argue in favor of the presence of the SST4 subtype in human placenta. At the doses administered, octreotide did not bind to placental somatostatin receptors. Our results may explain the absence of changes in both human placental GH and IGF-I concentrations that we observed during octreotide treatment.

Inhibition of growth and metastatic progression of pancreatic carcinoma in hamster after somatostatin receptor subtype 2 (sst2) gene expression and administration of cytotoxic somatostatin analog AN-238

“…Cell membranes were obtained from culture cells or from tumors as described (5,21), and somatostatin binding was performed after acid washing by using labeled [ 125…”

“…]somatostatin-14 as described (5,21). Binding assays were performed in triplicate in at least three separate experiments.…”

“…Total RNA was extracted by the guanidinium thiocyanate-phenol-chloroform method (9). RT-PCR was performed by using specific sense and antisense primers for rat preprosomatostatin, human sst2, and ␤ actin (9,11,21).…”

Pregnancy management in patients with acromegaly

“…In a large retrospective series, only three of 27 cases (11%) [22] exhibited radiological evidence of tumor growth during pregnancy. Tumor enlargement may also be theoretically triggered by somatostatin receptor ligand discontinuation at pregnancy onset [27]. However, as the pituitary gland enlarges during gestation due to hyperplasia of lactotrophic cells, pregnant patients with macroadenomas may also develop visual symptoms and/or headache as a result of the pituitary enlargement in a restricted sellar space [28].…”

“…The relatively uneventful course of pregnancy and delivery and the healthy newborns is usual. The literature indicates an increased risk of gestational diabetes and gravid hypertension in women with non-controlled GH/IGF1 hypersecretion before gestation [1,2,7,27], which must be appropriately treated, but in most patients, specific acromegaly therapy can be delayed until after delivery.…”