Placental Lactogen Concentrations Research Articles

A Randomized Controlled Trial of Complete Bed Rest versus Ambulation in the Management of Proteinuric Hypertension during Pregnancy

The authors have previously investigated the effect of bed rest versus ambulation on maternal disease in patients with proteinuric hypertension. They found that complete bed rest appeared to have no advantage over “ambulation as desired.” In the present report, they examine the comparative effects of rest and ambulation on fetoplacental well-being and fetal outcome in the same patients. Forty patients were divided into two groups (rested and ambulatory) of 20 patients each. Initially, the human placental lactogen concentrations were similar in the two groups, but the estriol concentrations were an average of 155 nmol per liter lower in the ambulant group. The difference between the means is not quite significant at the 5 per cent level (t = 2.019). With both the human placenta lactogen and estriol assays, there was a tendency for values to rise more in the group of patients managed by complete bed rest, but none of the differences shown between the groups approached significance. Among the 40 patients who participated in the trial were 10 who had both elevated plasma urate concentrations (more than 0.25 mmol per liter before 32 weeks, or more than 0.35 mmol per liter from 32 weeks) and grossly small-for-date fetuses on clinical examination. Strict bed rest in these 10 patients seemed to be associated with development of severe preeclampsia and better fetal prognosis. Four patients' fetuses died in utero from simple placental insufficiency. Another intrauterine death was caused by placental abruption at 30 weeks in a mildly hypertensive patient in the ambulant group. An early neonatal death caused by a tentorial tear during a spontaneous vaginal delivery at term occurred in a patient in the rested group. In both of these patients, plasma urate concentration was normal, and there was no evidence of fetal growth retardation. Of the 10 patients with both hyperuricemia and growth-retarded fetuses, the five patients who were confined to bed developed the premonitory symptoms of eclampsia (increasing headache, visual disturbances, epigastric pain, and vomiting), whereas only one of the patients allowed to ambulate freely in the ward did so. The development of premonitory symptoms led to urgent delivery by cesarean section in all except one of these patients. This one patient had a uterine size equivalent to only 23 weeks at 26 weeks of gestation and was treated conservatively for preeclampsia until fetal death supervened and was followed shortly by the onset of labor. The three remaining macerated stillbirths were in the ambulatory group. All of the birth weights for the 10 patients were below the 10th centile. The trial took place during 1978 and 1979. Since then, all but one of the patients who lost their babies while on the trial have been delivered near term of healthy babies after entirely normotensive pregnancies. The exception is the patient whose stillbirth was due to abruptio placentae. This patient remains mildly hypertensive, and a further pregnancy ended in miscarriage at 18 weeks.

The importance of prolactin for initiation of lactation in the pregnant ewe.

A single injection of ergocryptine (0.5 mg/kg liveweight) given to ewes 0.5-20 days prepartum or two injections (0.5 mg/kg liveweight per injection) given c. 30 and 10 days prepartum reduced concentrations of plasma prolactin to negligible (less than 5 ng/ml) values for 4 weeks after parturition, but did not affect concentrations of growth hormone and placental lactogen. Milking of treated ewes had no effect on concentrations of plasma prolactin during the first 4 weeks of lactation, but concentrations of growth hormone were increased during the 10-20 min period after milking. The half-life of prolactin in plasma was estimated as 21 min. In spite of the dramatic effect of ergocryptine on plasma prolactin all treated ewes secreted copious quantities of milk of normal composition. Mean daily yields of ewes treated with ergocryptine were not significantly different (P greater than 0.05) from those of untreated control ewes, but the mean +/- s.e.m. of total milk production over the first 3 weeks of lactation for ergocryptine-treated ewes was significantly lower (P less than 0.05) than that of control ewes (9.5 +/- 1.11 v. 14.1 +/- 1.20 kg milk). The results suggest that prolactin is not an essential component of the lactogenic and galactopoietic complexes of hormones in the ewe.

Temporal concentrations of rat placental lactogen in the peripheral circulation.

Placental lactogen (PL) is an abundant placental protein identified in several species, but to date little is known of mode or control of PL secretion. In the present study we sought to define the minute-to-minute variation in rat PL (rPL) secretion in late pregnancy by repeated blood sampling over a 3-h period. The results indicate that rPL may be secreted in an episodic pulsatile manner similar to the pulsatile secretion of pituitary prolactin (Prl) and growth hormone (GH). This evidence suggests a highly regulated dynamic control of secretion of a placental hormone.

Metabolic control and serum hormone levels in relation to retinopathy in diabetic pregnancy

The occurrence and progression of retinopathy were related to the mean blood glucose levels and the serum concentrations of prolactin, human placental lactogen, oestradiol and progesterone in 57 pregnant insulin-dependent diabetic patients. Fifteen patients had frank retinopathy, of whom eight showed a marked increase in retinopathy. The initial blood glucose levels were significantly higher in patients whose retinopathy progressed, whereas during the second and third trimester similar blood glucose levels were achieved in all groups. Serum concentrations of progesterone and human placental lactogen were significantly increased in diabetic patients during the last trimester when compared with those in normal pregnancies, and during the second trimester, patients with retinopathy showed significantly higher concentrations than those without, but no significant difference was found in oestradiol values. The eight patients with progressive retinopathy showed progesterone, human placental lactogen and oestradiol levels at or above the upper limit of the normal range. Throughout gestation, serum prolactin concentrations were significantly lower in diabetic patients than in healthy subjects. No correlation was found between serum prolactin values and the occurrence of retinopathy.

Effect of streptozotocin on foetal lambs in mid-pregnancy.

Streptozotocin was administered to 11 foetal lambs in utero at 70-85 days of gestation. Four of the foetuses survived and, when delivered at 134-142 days, exhibited significant growth retardation of the trunk and delayed osseous maturation in limb bones. The foetal kidneys and livers were most affected, but in three of the four foetuses, the weight of the brain was appropriate for gestational age. Likewise head size, measured by length or biparietal diameter, was normal. The insulin content of the foetal pancreas was less after streptozotocin-treatment than in normal animals of a similar gestation. Two streptozotocin-treated foetuses, catheterized at 120 days gestation, had higher glucose concentrations and lower insulin responses than in controls when infused with glucose. Plasma concentrations of ovine placental lactogen were lower in streptozotocin-treated foetuses than in controls, but serum somatomedin-like activity measured by receptor assay was greater than in controls. When the foetal serum was chromatographed on Sephadex G150 at acid pH, the major size about 10000). The foetal growth retardation associated with streptozotocin administration in mid-pregnancy may be due to insulin deficiency, but the normal brain weight which occurred suggests that some other factor (possibly a somatomedin) regulates the growth of this organ.

Secretion of placental lactogen, growth hormone, and prolactin in late pregnant rats.

The secretory patterns of placental lactogen (PL), GH, and PRL were determined in conscious unrestrained late pregnant rats by measurement of the plasma concentrations of each hormone by RIA. Blood samples were collected over a 4-h period at 15-min intervals on days 18 and 19 of gestation. From days 18-19, GH levels increased 2-fold, no change was observed in PRL levels, while PL concentrations increased slightly. There was an ultradian rhythm present in GH and PRL secretion, with a frequency of two to three secretory spikes per 4-h collection period. The variable concentrations of PL in the peripheral circulation were suggestive of an episodic or ultradian secretory pattern. PL levels increased 100% or more within 30 min (i.e. from 485 to 1132 ng/ml) or decreased as much as 65% within 60 min (i.e. from 792 to 247 ng/ml). The relative magnitude of these changes were similar to, but not coincident or correlated with, those for GH.

The relationship between breed and litter size in sheep and maternal serum concentrations of placental lactogen, estradiol and progesterone.

Milk production in sheep is known to be affected by breed and litter size. To investigate a possible hormonal basis for such effects, we measured maternal serum concentrations of placental lactogen, estradiol and progesterone during late gestation in sheep of several breeds and ages. Circulating concentrations of placental lactogen were directly related to litter size in all breeds, with the greatest concentrations being observed in Finnish Landrace ewes bearing three lambs. Among monotocous animals, no significant breed differences were observed, but ewe lambs bearing crossbred fetuses had higher placental lactogen concentrations than ewes of the same breed carrying purebred offspring. Placental lactogen concentrations were similar in all animals bearing twins, except for Corriedale ewes, which had the lowest concentrations. Serum estradiol concentrations 2 to 5 weeks prepartum did not differ between ewes of different breeds or ewes with different litter sizes. Progesterone, like placental lactogen, was related to litter size and, presumably placental mass. The relationship between litter size and placental lactogen concentrations, together with the absence of difference in estradiol secretion, suggests that differences in production of the lactogenic hormone may contribute to the superior lactational performance that has been reported for ewes which bear multiple offspring.

Fetal and material ovine placental lactogen during hyperglycaemia, hypoglycaemia and fasting.

Hyperglycaemia was produced in chronically catheterized fetal lambs and pregnant-ewes by the infusion of glucose into the fetus. Plasma concentration of placenta lactogen did not change significantly in either fetal or maternal circulation. Fetal and maternal hypoglycaemia was induced by administration of insulin to the fetus and ewe separately. Plasma concentrations of placental lactogen in the fetus did not change significantly but maternal plasma concentrations fell slightly after hypoglycaemia in either fetus or ewe. Plasma concentrations of placental lactogen rose in both the ewe and fetus during prolonged fasting of the ewe. These results neither confirm nor refute a role for placental lactogen in intermediary metabolism of the pregnant ewe and fetus but glucose concentration alone is unlikely to be a significant factor in the control of secretion of this hormone.

Uterine and peripheral blood concentrations of human chorionic gonadotropin and human placental lactogen

One hypothesis is that two placental protein hormones (human placental lactogen and human chorionic gonadotropin) are effective immunosuppressive agents that prevent the rejection of a fetus because of their very high concentrations. In patients undergoing elective repeat cesarean sections at term, we measured the concentrations of these hormones in blood obtained simultaneously from draining ovarian veins and peripheral veins, and found no significant differences.

Epidermal growth factor: a critical factor in fetal maturation?

Epidermal growth factor (EGF) infused over 3-14 days into fetal sheep of 110-125 days gestation resulted in a number of morphological and endocrine changes. Striking hypertrophy of the skin, wool follicles and their accessory structures was seen, together with a reduction in the ratio of secondary to primary follicles and degenerative changes in wool fibres associated with shedding of fibres. Adrenal, thyroid, liver and kidney weights were increased while thymus weight was decreased. The increase in adrenal size resulted from cortical hypertrophy and was associated with increased cortisol secretion. Thyroid hypertrophy was accompanied by an increase in colloid stores, decreased plasma thyroxine and reverse triiodothyronine (T3) concentrations, unchanged plasma T3 and thyroid-binding globulin and raised thyrotropin (TSH) levels. Thyrotropin receptor affinity and content per gram of tissue were unchanged. Fetal and maternal plasma prolactin and growth hormone levels, and fetal plasma placental lactogen levels, were unchanged, although there was a significant rise in maternal plasma placental lactogen concentrations with high doses of EGF. Other maturational parameters such as switching from fetal to adult haemoglobin and liver glycogen content were unaffected.

Placental lactogen in the goat in relation to stage of gestation, number of fetuses, metabolites, progesterone and time of day.

Placental lactogen has been measured in goats throughout pregnancy by radioreceptor assay of prolactin-like activity. Lactogenic activity, which is not prolactin, increased from less than 5 nmol/l in week 8 to 27 nmol/l by week 16. There was no further change until term. Plateau concentrations (week 16 to term) were highest in animals carrying triplets, 49.5 nmol/l. There were marked functuations in placental lactogen over a 24 h period. These short-term fluctuations were not related to changes in glucose, non-esterified fatty acids or, in two animals, progesterone. However, there was a negative correlation between mean concentrations of placental lactogen and glucose in plasma of 20 goats sampled over a 24 h period between weeks 15 and 20 of gestation. There was no difference in placental lactogen concentration from week 16 to term between goats in their first and second pregnancies although the normal period of increase in placental lactogen was delayed by some 3 weeks in goats in their second pregnancy. In hemimastectomized goats, hypophysectomy on day 60 did not affect placental lactogen but daily treatment with bromocriptine (5 mg/day) from day 60 to day 120 blocked the normal rise in concentration.

Circulating choriogonadotropin β subunit in a patient with primary amenorrhea and embryonal ovarian carcinoma

A 20-year-old patient, phenotypically female, genotypically male, who had previously sought medical attention for primary amenorrhea, developed an embryonal carcinoma in the right gonad. Selective formation of the β subunit of choriogonadotropin was demonstrated by positive test results on native serum and after gel filtration with a classical “β-HCG” assay and a specific assay for the β subunit, but negative results with a specific assay for choriogonadotropin. The concentrations of placental lactogen, α-fetoprotein and choriogonadotropin α subunit were normal. This case illustrates the necessity for early diagnosis of primary ovarian insufficiency in cases of primary amenorrhea. The results indicate that, for the detection of certain neoplastic disorders, the lower specificity of the choriogonadotropin assay introduced in 1972 by Vaitukaitis and coworkers [25] -reacting equally well with choriogonadotropin and with free β subunit — may have advantages over the more specific assays for choriogonadotropin and for the β subunit described by Franchimont et al. [8,28,29]. The availability of the latter assays, however, facilitates the identification of the immunoreactive material found with the former assay. The ambiguity of the present nomenclature for “β-HCG” assay is pointed out.

Concentrations of placental lactogen in chronically catheterized ewes and fetuses in late pregnancy.

The concentration of ovine placental lactogen (oPL) was measured by radioimmunoassay in plasma samples from chronically catheterized ewes and their fetuses from day 110 of gestation to term (about day 145). Concentrations of oPL in the plasma of the mother and fetus were raised after surgery, and remained raised for 3--5 days after the operation. Concentrations of oPL were greatest in the fetus at days 120--124 of gestation, and then declined until delivery. Mean concentrations of oPL in the fetus in late pregnancy for single, twin and triplet pregnancies were 101 +/- 6 (S.E.M.), 100 +/- 11 and 115 +/- 59 ng/ml respectively and were not significantly different. Mean concentrations of oPL in the mother in late pregnancy for single, twin and triplet pregnancies were 718 +/- 227, 1387 +/- 160 and 1510 +/- 459 ng/ml respectively; the difference between these means was significant (P less than 0.05). Peak concentrations were noted at days 130--139 of gestation after which concentrations fell and were significantly lower on the day of delivery (P less than 0.01). Concentration of oPL in the mother showed no circadian rhythm. The mean concentrations of oPL in maternal plasma during late pregnancy was significantly correlated to the combined fetal weight at birth (r = 0.624, P less than 0.01).

Urinary estrogen excretion and concentration of serum human placental lactogen in pregnancies following legally induced abortion.

Feto-placental function was assessed by 24-hour excretion of estrogen in urine and by the concentration of human Placental Lactogen (hPL) in serum in pregnant women whose previous pregnancy was terminated by legally induced abortion. The mean 24-hour excretion of estrogens in urine and the mean concentration of hPL in serum were no lower in this group than in women without previous induced abortion. Neither was the frequency of a low 24-hour excretion of estrogens in urine or low concentration of hPL in serum (values less than mean - 1.96 s) found to be increased. This study could not demonstrate an increased frequency of dysfunction of the feto-placental unit during the last part of pregnancy in women with previous legally induced abortion. These findings indicate that legal abortion does not seem to increase the frequency of retarded intrauterine growth in a subsequent pregnancy.

A Prospective Evaluation of Placental Lactogen as a Test for Neonatal Risk

This study evaluates the usefulness of maternal serum concentrations of human placental lactogen in the management of high-risk pregnancies. The study was performed in a community hospital over a year’s time and involved 250 gestations. The test detected only 11.4% of the pregnancies defined as high-risk by clinical criteria and none of the pregnancies in which the newborn was compromised. Serum human placental lactogen is an insensitive test in predicting the outcome of pregnancies in an obstetric population unless historical information regarding maternal disease is unavailable.

The application of immunoperoxidase methodology for the visualization of prolactin binding sites in human prostate tissue

In previous studies the immunoperoxidase method was used to detect intracellular prolactin binding sites in epithelial cells of normal and neoplastic rat prostate. As an extension of this work, the same approach was used to test for and to localize prolactin binding sites in autopsy and biopsy specimens of formalin fixed, paraffin embedded human prostate. Rehydrated tissue sections were exposed to varying concentrations of human placental lactogen or human prolactin and then to human placental lactogen or human prolactin antisera. The loci of hormone binding were visualized by an immunoperoxidase staining sequence. Hormone pretreatment produced immunospecific, dose related staining inside epithelial cells of normal, hyperplastic, and neoplastic human prostate indicative of intracellular prolactin binding. The patterns of intracellular hormone binding in human prostate were similar to those seen previously in rat prostate tissue. The possible involvement of prolactin in prostatic cancer and the potential diagnostic value of the immunoperoxidase approach to hormone binding are discussed.

MAMMARY GROWTH DURING PREGNANCY IN HYPOPHYSECTOMIZED OR BROMOCRIPTINE-TREATED GOATS

Mammogenesis in primiparous hypophysectomized goats has been assessed between days 60 and 120 of gestation and compared with that found in untreated goats and goats treated with 5 mg bromocriptine/day. There were fivefold increases in the weight of lobulo-alveolar tissue in the hypophysectomized and bromocriptine-treated goats and a tenfold increase in the untreated goats. Histological examination of the mammary glands at 120 days showed normal structure, and determinations of lactose, lactose synthetase, cytosol enzymes, protein, DNA and RNA indicated qualitatively normal initiation of milk synthetic capabilities in both the hypophysectomized and bromocriptine-treated goats. Bromocriptine treatment lowered the plasma concentration of placental lactogen as well as that of prolactin. The results indicate that placental lactogen has important mammogenic effects during pregnancy.

A Prospective Evaluation of Placental Lactogen as a Test for Neonatal Risk

This study evaluates the usefulness of maternal serum concentrations of human placental lactogen in the management of high-risk pregnancies. The study was performed in a community hospital over a year's time and involved 250 gestations. The test detected only 11.4% of the pregnancies defined as high-risk by clinical criteria and none of the pregnancies in which the newborn was compromised. Serum human placental lactogen is an insensitive test in predicting the outcome of pregnancies in an obstetric population unless historical information regarding maternal disease is unavailable.

Stimulation of ovine placental lactogen secretion by arginine infusion.

Arginine has been demonstrated to be a potent stimulus to GH and PRL secretion. To determine the effect of arginine on plasma ovine placental lactogen (oPL) concentrations, arginine (50 g in 350 ml distilled water, pH 7.4) or hypertonic saline of identical volume, osmolality, and pH was infused iv over a 30-min period into nine pregnant ewes, and blood samples from chronic indwelling venous catheters were obtained at frequent intervals before and for 8 h after the infusions. After the infusion of hypertonic saline, plasma oPL concentrations (measured by homologous RIA) decreased 20--50% over 1--2 h and then returned to baseline concentrations. After the infusion of arginine, plasma oPL concentrations also decreased by 20--50% for 1--2 h. However, 2--3 h after the infusion, plasma oPL concentrations in creased 79--115% (delta = 204--700 ng/ml) over preinfusion concentrations in seven ewes and 454% (2930 ng/ml) and 1142% (2042 ng/ml) in two ewes and remained elevated for the remainder of the 8-h interval. When the amount of arginine infused was reduced from 50 to 25 g, an increase in plasma oPL concentrations occurred in only one of five ewes. Plasma oPL concentrations increased by 8--58% after infusions of 50 g alanine or glycine but did not increase after 50 g glutamic acid. The delayed oPL response to arginine suggests that the increase in plasma oPL concentrations is not caused directly by arginine but rather by changes in the synthesis, secretion, and/or degradation of oPL induced indirectly by arginine.

Plasma steroid changes in pre-term labour in association with salbutamol infusion.

Serial measurements of peripheral plasma concentrations of progesterone and oestradiol-17beta were made in 23 women with singleton pregnancies who were given intravenous salbutamol in an attempt to inhibit pre-term labour. Mean levels of both hormones fell significantly during salbutamol infusion but returned to pre-treatment levels after therapy was stopped. Plasma human placental lactogen concentrations did not change during salbutamol infusion, suggesting that the fall in steroid hormone levels was unlikely to be an effect of altered uterine or placental blood flow.