Henry G. Friesen

Radioreceptor assay for prolactin and other lactogenic hormones

A radioreceptor assay with a sensitivity of 5 nanograms per milliliter has been developed for mammalian and avian pituitary prolactin, placental lactogenic hormones, and humnan growth hormone, using a membrane receptor preparation isolated from rabbit mammary glands. Prolactin preparations inhibited the binding of [125I]prolactin to receptors in direct proportion to the biological potency of these preparations. Thus, the radioreceptor assay provides a convenient and simnple assay for hormones which have lactogenic activity.

Studies of prolactin secretion in human pregnancy

n Recent studies have confirmed the presence of a separate (HPr) human prolactin molecule. Measurement of HPr concentrations has been performed in normal and abnormal gestation and during the menstrual cycle. HPr rises throughout gestation with a return to prepregnant concentrations by the 7th postpartum day. Variable increases in plasma prolactin were observed after intravenous administration of arginine, especially after the 30th week of gestation. Puerperally, prolactin rises in response to sucking. Amniotic fluid prolactin levels are 100 times those of maternal or fetal blood. No significant change in basal HPr is seen during the menstrual cycle. The ability to measure this new pituitary polypeptide by radioimmunoassay permits investigation of its role in human gestation.n

Factors influencing the secretion of human prolactin and growth hormone in menstrual and gestational women

Human pituitary prolactin (PRL) is released in a pattern that is different from growth hormone (HGH). Basal PRL concentrations remain unchanged throughout the menstrual cycle and bear no apparent relationship to the cyclic change in gonadotropins. Significant increases in PRL occur after intramuscular chlorpromazine (CPZ). The response is dose related. These results correlate with PRL values measured in patients ingesting large amounts of phenothiazines for psychiatric disease. Thyrotropin-releasing hormone (TRH) provokes the release of PRL as well as thyroid-stimulating hormone (TSH). TRH-induced PRL release during menses is similar to that found at midcycle. On the other hand, HGH secretion remains unaffected by CPZ and TRH. Throughout pregnancy, basal plasma PRL rises to a mean of 214 ng. per milliliter at term. In spite of this, PRL levels rise even higher in response to intravenous TRH. Postpartum, puerperal PRL levels increase in response to nursing and intravenous TRH but not after intranasal oxytocin. The post-TRH response can be dissociated from the PRL response to nursing especially beyond 60 postpartum days. Elevations in endogenous PRL secretion are followed by changes in breast function within three hours. These changes include engorgement with increased milk production and letdown. No such changes occur after intravenous TRH in pregnancy. Intravenous TRH appears to be a specific stimulus to PRL release and is without significant side effects. These studies suggest that PRL may promote breast milk production in lactating women. The mammary response to elevated PRL concentrations may be modified, however, by the concentration of endogenous estrogen and progesterone since no breast engorgement followed the post TRH-PRL rise before delivery. There is no similarity between the secretion of PRL and HGH in pregnancy.

COMPARISON OF THE EFFECT OF APOMORPHINE AND l‐DOPA ON SERUM GROWTH HORMONE LEVELS IN NORMAL MEN

Apomorphine hydrochloride (0.75 mg s.c.) has been compared with l‐dopa (500 mg p.o.) in their effects on growth hormone secretion in a double blind cross‐over study involving nine healthy men. Apomorphine increased serum GH levels above 10 ng/ml in all nine subjects 30–60 min after injection. In contrast, only six of these subjects showed a similar elevation with l‐dopa and in only three had the level increased above 6 ng/ml by 60 min. One subject failed to respond to l‐dopa and in two others the peak was less than 6 ng/ml. GH levels were significantly higher at 30, 45 and 60 min following apomorphine than following l‐dopa. Apomorphine‐induced GH release was not related to changes in serum cortisol or blood sugar. Benztropine mesylate (1 mg i.m.) had no effect on apomorphine‐induced GH release. These results suggest: (a) apomorphine may have advantages over l‐dopa as a provocative agent to assess GH secretory capacity; (b) a dopaminergic mechanism subserves GH secretion; (c) cholinergic mechanisms do not antagonize dopaminergic‐related GH release.

Current understanding of human prolactin physiology and its diagnostic and therapeutic applications: A review

Human prolactin has been measured with a sensitive and specific radioimmunoassay in normal subjects and shows little variation with age or sex. High levels have been found in the sera of pregnant women and infants up to 6xa0weeks of age, as well as in amniotic fluid. Prolactin secretion is predominantly under inhibitory control by the hypothalamus. The release of prolactin-inhibitory factor is regulated by dopaminergic fibers. Stress, exercise, certain tumors, and drugs (thyrotropin-releasing hormone, phenothiazines) increase prolactin secretion, while l -dopamine and ergot compounds (CB-154) lower it. This information is now being applied to several diagnostic and therapeutic problems. Prolactin stimulation and suppression tests as an index of hypothalamic and pituitary function have been developed. Drug therapy for galactorrhea which results in the suppression of prolactin has been explored. Attempts to increase milk volume as well as protein and fat content in lactationally deficient mothers by increasing the prolactin concentration have been carried out.

Breast-Feeding: Effects on the Hypothalamic Pituitary Gonadal Axis

Regularly breast-feeding women had increased serum prolactin, low estradiol and reduced gonadotropin responses to luteinizing hormone-releasing hormone during the first 6 weeks postpartum. women who started intermittent breast-feeding (BF±) after the third week did not sustain these hormonal patterns. Non-nursing (NN) women had hormonal values in the follicular range by the third week. Menses resumed within 6 to 12 weeks in NN and BF± women whereas amenorrhea persisted beyond the 14th week in the regularly breast-feeding women. The persistent hormonal changes associated with regular breast-feeding may account for the prolonged amenorrhea.

Failure of β-endorphin antiserum, naloxone, and naltrexone to alter physiologic growth hormone and insulin secretion

Abstract The role of endogenous opiate-like peptides in physiologic regulation of growth hormone (GH) and insulin (IRI) secretion was assessed by passive immunization with β-endorphin antiserum and by administration of the opiate antagonists naloxone and naltrexone. Six-hour secretory profiles were obtained from 5 groups of freely-moving chronically cannulated male rats following the i.v. administration of (I) β-endorphin antiserum, (II) normal rabbit serum, (III) naloxone (1 mg/kg), (IV) naltrexone (1 mg/kg), and (V) normal saline. The typical ultradian rhythm of GH secretion was evident in all groups with most peak GH values >400 ng/ml. No disruption in amplitude of periodicity of the GH rhythm was observed and there was no significant difference in mean 6-hr plasma GH levels. Plasma IRI levels fluctuated minimally over the 6-hr sampling period. There was no significant difference in mean 6-hr IRI levels between groups I and II, or between groups III, IV and V. These data do not support the view that endogenous opiate-like peptides play a physiologically important role in maintaining basal GH and IRI secretion.

The Subcellular Distribution of Human Placental Lactogen

In 1962 Josimovich and MacLaren (1) reported that the human placenta and retroplacental serum contain a lactogenic substance immunologically related to growth hormone. In the intervening years there have been many studies on the chemistry, biological effects, and secretion (2–7) of human placental lactogen (HPL) but comparatively little investigation on its intraplacental site of synthesis and storage. Sciarra (8) in an excellent review considered the evidence for the placental and cellular origin of HPL. He reported earlier that rabbit anti-HGH serum labeled with fluorescein isothiocyanate was limited to the syncytiotrophoblast layer of the villous epithelium (9). This communication describes the subcellular localization of HPL and outlines a simple method for its purification from fresh placentas.