Heterogeneity of pituitary and plasma prolactin in man: decreased affinity of big prolactin in a radioreceptor assay and evidence for its secretion
Molecular heterogeneity of immunoreactive human PRL (IR-hPRL) plasma was assessed by exclusion chromatography in blood from 4 normal adults, 3 newborn infants, 2 late gestational women, 3 patients with primary hypothyroidism and high PRL levels, 2 with functional hyperprolactinemia, 3 with acromegaly, and 10 with PRL-secreting tumors. Three forms of PRL were detected: big-big hPRL, big hPRL, and little hPRL. In normal subjects, the proportion of big-big, big, and little hPRL components was 5.1%, 9.1%, and 85.8%, respectively, without change in the distribution after TRF stimulation. In 8 of 10 patients with PRL-secreting tumors, we detected a significantly higher proportion of big PRL. In 2 additional patients with prolactinomas, the proportion of big PRL was much higher. In 3 of 10 patients, the molecular heterogeneity of the tumor PRL was similar to that in plasma. In 1 acromegalic, there was a very high proportion of big-big hPRL. The PRL fractions were tested in a radioreceptor assay (RRA) using membranes from rabbit mammary gland. Big PRL was much less active than little PRL in the RRA. The fractions were rechromatographed after storage. Big PRL partially distributed as little or big-big PRL, while little PRL remained unchanged. Big-big PRL from tumor extract partially converted into big and little PRL. The big PRL obtained by rechromatography had low activity in the RRA. These observations suggest at least part of the receptor activity of big PRL may arise from generation of or contamination by little PRL. The decreased binding affinity of big PRL in the RRA also indicates that big PRL has little, if any, biological activity. The evidence suggests big PRL is a native PRL dimer linked by intermolecular disulfide bonds which arises in the lactotrope as a postsynthetic product or derivative and is not a true precursor prohormone.
- Research Organization:
- Univ. of California, San Francisco
- OSTI ID:
- 5876106
- Journal Information:
- J. Clin. Endocrinol. Metab.; (United States), Vol. 47:6
- Country of Publication:
- United States
- Language:
- English
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62 RADIOLOGY AND NUCLEAR MEDICINE
ENDOCRINE DISEASES
LTH
MOLECULAR WEIGHT
RADIOASSAY
SECRETION
ACROMEGALY
BINDING ENERGY
BLOOD PLASMA
HYPOTHYROIDISM
IMMUNE REACTIONS
INFANTS
LIQUID COLUMN CHROMATOGRAPHY
MAMMARY GLANDS
MAN
METABOLISM
NEOPLASMS
PITUITARY HORMONES
PREGNANCY
RABBITS
SIZE
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BODY
BODY FLUIDS
CHILDREN
CHROMATOGRAPHY
DISEASES
ENERGY
GLANDS
GONADOTROPINS
HORMONES
MAMMALS
NEONATES
ORGANS
PEPTIDE HORMONES
PRIMATES
SEPARATION PROCESSES
VERTEBRATES
551000* - Physiological Systems
551001 - Physiological Systems- Tracer Techniques
550600 - Medicine
550601 - Medicine- Unsealed Radionuclides in Diagnostics