The ontogenesis of human fetal hormones. III. Prolactin

Abstract

The synthesis and release of human prolactin (hPRL) in the human fetus was assessed by radioimmunoassay analysis of the content and concentration of hPRL in 82 pituitary glands and the concentration of serum hPRL in 47 fetuses of gestational age 68 days to term. Fetal hPRL exhibited parallelism with the reference standard (Lewis 203-1). hPRL was detected by 68 days of gestation (10 wk), the earliest fetal pituitary gland studied; 8 out of 33 pituitaries had a prolactin (PRL) content above 2.0 ng between 10-15 wk gestation. The mean content of PRL in the pituitary gland increased sharply from 14.8 ± 4.6 ng at 15-19 wk to 405 ± 142 ng at 20-24 wk and 542 ± 204 ng at 25-29 wk gestation. By term, the mean content was 2,039 ± 459 (range 493-3,689) and the mean concentration 15.9 ± 2.4 ng/mg (range 7-20). There was a significant positive correlation (P < 0.001) between the hPRL and human growth hormone (hGH) content of fetal pituitary glands; at term the hPRL/hGH ratio was 1/290. The concentration of serum hPRL between 12 and 24 wk ranged from 2.9 to 67 ng/ml, mean 19.5 ± 2.5 ng/ml (n = 41); by 26 wk fetal serum hPRL increased sharply and attained levels of 300-500 ng/ml in late gestation. At delivery, mean plasma concentration of hPRL was 167 ± 14.2 ng/ml in 36 umbilical venous specimens and 111.8 ± 12.3 ng/ml in the matched maternal venous specimens. No correlation between serum hPRL and the pituitary content or concentration of hPRL was demonstrable in 12 matched fetal specimens. In five anencephalic infants, umbilical venous hPRL levels were between 65 and 283 ng/ml. In two anencephalic infants, thyrotropin releasing factor (TRF) (200 μg IV) evoked a rise in serum hPRL in one patient from 43 to 156 ng/ml at 30 min, and in the other from 65 to 404 ng/ml at 120 min. In both patients, plasma thyroid stimulating hormone (TSH) rose from undetectable base line levels to peak levels of 97 and 380 μU/ml, respectively. The pattern of change in serum hPRL in the human fetus contrasts sharply with that of serum hGH, luteinizing hormone, or follicle stimulating hormone. These observations in the fetus and in anencephalic infants suggest that the striking elevation of serum PRL in the fetus is neither mediated by a putative PRL releasing factor or by TRF, nor is a consequence of suppression or absence of PRL release inhibiting factor alone, as a functional hypothalamus is not required to attain the high PRL concentration at term. Several lines of evidence support the view that high plasma estrogen levels characteristic of gestation act directly on the fetal anterior hypophysis to stimulate PRL secretion or to sensitize the secretory mechanism of the lactotrope, increasing its responsiveness to other stimuli.