Expression of somatostatin receptor SST4 in human placenta and absence of octreotide effect on human placental growth hormone concentration during pregnancy.
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 mumol/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.
Caron
P
P
Service d'Endocrinologie et Maladies Métaboliques, Institut Louis Bugnard, Toulouse, France.
Buscail
L
L
Beckers
A
A
Estève
J P
JP
Igout
A
A
Hennen
G
G
Susini
C
C
D000236:Adenoma / Q000188:drug therapy / Q000378:metabolism; D000328:Adult; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015282:Octreotide / Q000009:adverse effects* / Q000627:therapeutic use; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000188:drug therapy*; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism
D017481:Receptors, Somatostatin; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013972:Thyrotropin; D015282:Octreotide