Endocrine regulation of fetal development and its relation to parturition in the rhesus monkey.

Rhesus monkey fetuses were surgically prosencephalectomized (Type 2) or functionally hypophysectomized (Type 1) at 75 days gestation, then returned to the uterus until elective Caesarean section on day 145--150 (term 167 days). Deprivation of fetal hypothalamic releasing factors in Type 2 and fetal pituitary tropic hormones in Type 1 significantly delayed the ontogeny and functional development of fetal endocrine tissues. Bone ossification and growth were significantly retarded in Type 1 only, not in Type 2. In Type 1 the body and all organs except the endocrine glands were about half normal weight. The adrenals, thyroids, ovaries and testes were histologically abnormal and about one-tenth normal weight. Non-endocrine organs were histologically similar to 110-130-day fetuses. Thyroxine (T4) concentrations were significantly depressed in Type 1 fetal and maternal plasma at Caesarean section but normal in Type 2. Cortisol concentrations were normal in Type 1 fetal and maternal plasma. Types 1 and 2 plasma oestradiol concentrations were significantly lower in mothers but normal in fetuses. Type 1 placentas produced significantly less progesterone in vitro than normal. Fetal endocrine autonomy is indicated (thyrotropin-releasing factor excepted). Many of the hypothalamic and anterior pituitary hormones do not pass in effective amounts from mother to fetus. Fetal endocrine autonomy is a prerequisite for the control of both development and parturition.

Effects of fetal decapitation on the structure and function of Leydig cells in rhesus monkeys (Macaca mulatta).

Fetal decapitation in utero has enabled us to study the role of fetal pituitary hormones in the development of the fetal testis. Testes from males decapitated near 80 days of gestational life and later delivered at 150 days were smaller than normal and about one-tenth the normal weight. The size of the seminiferous tubules was similar in both groups; however, the number of Leydig cells seemed reduced. In addition, the Leydig cells of the experimental group contained smaller mitochondria with reduced tubular cristae, fewer lipid droplets, and reduced agranular endoplasmic reticulum. Androgen production was inhibited. Measured by radioimmunoassay, the testosterone level in the umbilical vein was 329 +/- 82 pg/ml in six decapitates fetuses, 412 +/- 62 pg/ml in ten normal fetuses. The level in the umbilical artery was 328 +/- 56 pg/ml in five decapitated fetuses, 658 +/- 140 pg/ml in normal fetuses. These studies suggest that chronic deprivation of fetal pituitary hormones inhibits the growth and development of the testis in general and of the Leydig cells in particular.

A new method for determining liver microsomal cholesterol 7alpha-hydroxylase.

A method is described to determine the mass of 7alpha-hydroxy cholesterol synthetized in vitro by liver microsomes without the use of a radioactive substrate.

The effect of fetal hypophysectomy on placental biosynthesis of progesterone in rhesus.

Placental slices from intact rhesus fetuses were incubated without added substrate. The incubated tissue levels of progesterone (P4) differed according to the sex of the fetus. Slices from female placentas contained significantly more P4 than did those of males. The addition of pregnenolone (P5) to the incubation media caused tissue levels of P4 to increase 1.5 to 3 times control tissue levels for both female and male placentas. Moreover, the sex difference in P4 biosynthesis was eliminated by adding P5 to the incubations. Since control incubations of male placental tissue produced less P4 than those of females, the net increase in P4 synthesis with added P5 was greater for male than female placental tissue. These observations indicated that the step(s) in P4 biosynthesis which were affected by the fetal genotype lay between cholestrol and P5. Incubation of placental slices derived from decapitated fetuses secreted significantly less P4 into the incubation medium than those of intact fetuses. Moreover, the sex difference in the media content of P4 was eliminated. However, decapitation did not eliminate the sex difference in the tissue content of P4 during control incubations. When P5 was added to the incubations, media and tissue levels of P4 increased significantly over control levels for placentas from both sexes. However, the addition of P5 to the incubations from decapitated males did not restore P4 production in the tissue or the medium to levels observed for intact males. However, this did occur when P5 was added to incubations from decapitated females. It appears that fetal decapitation decreased cholesterol side chain cleaving activity and delta5-3beta-hydroxy-steroid dehydrogenase content of the placenta. These data indicate that hormones of fetal origin may control P4 production by the placenta.