title: Hypophysectomy of the fetal lamb leads to a fall in the plasma concentration of insulin-like growth factor I (IGF-I), but not IGF-II.
abstract: The role of the pituitary gland in the regulation of the plasma concentrations of insulin-like growth factors (IGFs) in the late gestation sheep fetus has been examined. Singleton sheep fetuses were either hypophysectomized or sham-operated between days 110-120 of gestation. Blood samples were then collected via carotid cannulae at least three times weekly for the remainder of gestation. In some hypophysectomized fetuses T4 was administered (100 g/day) to overcome the hypothyroidism caused by hypophysectomy. Blood samples were also obtained from lambs during the perinatal period, neonatal lambs within 1-10 days after birth, and pregnant and nonpregnant adult ewes. All plasma samples were subjected to Sephadex G-50 gel filtration under acidic conditions (pH 2.3) to eliminate IGF-binding protein activity. The fractions containing the free IGF peptides were collected and assayed for IGF-I by heterologous RIA, and IGF-II by a homologous RRA. Plasma concentrations of IGF-I and IGF-II did not change with advancing gestational age in any fetal group and were not affected by the prolonged gestation that results from hypophysectomy. The mean plasma IGF-I and IGF-II concentrations in the sham fetuses were 112 +/- 8 and 1340 +/- 112 ng/ml, respectively. Hypophysectomy without thyroid hormone replacement resulted in a significant decrease in plasma IGF-I concentrations to 50 +/- 5 ng/ml, whereas IGF-II concentrations were not affected (1096 +/- 124 ng/ml). IGF-I concentrations in the hypophysectomized fetuses that received T4 were significantly increased (67 +/- 6.0 ng/ml) compared to those in the hypophysectomized fetuses that did not receive T4. The IGF-II concentrations in the hypophysectomized fetuses that received T4 were similar to those in the sham-operated fetuses (1120 +/- 112 ng/ml). At term IGF-I concentrations were increased (180 +/- 21 ng/ml) and IGF-II concentrations were decreased (264 +/- 25 ng/ml) compared to fetal values. Plasma IGF-I concentrations in the prepubertal lamb were similar to the fetal values. Pregnancy in the adult ewe was associated with a significant increase in IGF-II, but had no effect on IGF-I plasma concentrations. These data show that circulating IGF-I concentrations in the fetal lamb are under some pituitary and thyroid control, whereas IGF-II concentrations are independently of pituitary or thyroid status. We confirm, using a homologous assay, that fetal IGF-II concentrations are high and then decrease at term. These data also support the concept that a pregnancy-related factor may regulate plasma IGF-II concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Mesiano
authors.forename: I R
authors.initials: IR
authors.lastname: Young
authors.forename: A W
authors.initials: AW
authors.lastname: Hey
authors.forename: C A
authors.initials: CA
authors.lastname: Browne
authors.forename: G D
authors.initials: GD
authors.lastname: Thorburn
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000097:blood; D002850:Chromatography, Gel; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005865:Gestational Age; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000097:blood*; D007335:Insulin-Like Growth Factor II / Q000097:blood*; D010902:Pituitary Gland / Q000196:embryology* / Q000502:physiology; D011247:Pregnancy; D011863:Radioimmunoassay; D011869:Radioligand Assay; D012756:Sheep; D013002:Somatomedins / Q000097:blood*; D013974:Thyroxine / Q000494:pharmacology
chemical_list: D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013974:Thyroxine