There is currently widespread interest in the IGFs (IGF-I and IGF-II) and their roles in the regulation of growth and differentiation of an ever increasing number of tissues are being reported. This selective review focused on the current state of our knowledge about the structure of mammalian IGFs and the multiple forms of mRNAs which arise from alternative splicing and promoter sites which arise from gene transcription. Current progress in the immunological measurement of the IGF is reviewed including different strategies for avoiding binding protein interference. The results of measurements of serum IGF-I and IGF-II in fetus and mother and at various stages of postnatal life are described. Existing knowledge of the concentration of these peptides in body fluids and tissues are considered. Last, an attempt is made to indicate circumstances in which the IGFs are exerting their actions in an autocrine/paracrine mode and when endocrine actions predominate. In the latter context it was concluded that an important role for GH action on skeletal tissues via hepatic production of IGF-I and endocrine action of IGF-I on growth cartilage is likely.

Insulin-Like Growth Factors I and II. Peptide, Messenger Ribonucleic Acid and Gene Structures, Serum, and Tissue Concentrations

Nutrition is one of the main regulators of circulating IGF-I. In humans, serum IGF-I concentrations are markedly lowered by energy and/or protein deprivation. Both energy and proteins are critical in the regulation of serum IGF-I concentrations. Indeed, after fasting, optimal intake of both energy and protein is necessary for the rapid restoration of circulating IGF-I. We believe, however, that in adult humans energy may be somewhat more important than protein in this regard. While the lowest protein intake is able to increase IGF-I in the presence of adequate energy, there is a threshold energy requirement below which optimal protein intake fails to raise IGF-I after fasting. When energy intake is severely reduced, the carbohydrate content of the diet is a major determinant of responsiveness of IGF-I to GH. The essential amino acid content of the diet is also critical for the optimal restoration of IGF-I after fasting, when protein intake is reduced. The exquisite sensitivity of circulating IGF-I to nutrients, the nycthemeral stability of its concentrations and its relative short half-life constitute the basis for its use as a marker of both nutritional status and adequacy of nutritional rehabilitation. For these indications, IGF-I measurement is more sensitive and more specific than measurement of the other nutrient-related serum proteins (albumin, prealbumin, transferrin, retinol-binding protein). Animal models have been developed to investigate the mechanisms responsible for the nutritional regulation of IGF-I. There is no doubt that many mechanisms are involved (Fig. 12). Decline of serum IGF-I in dietary restriction is independent of the diet-induced alterations in pituitary GH secretion. The role of the liver GH receptors is dependent on the severity of the nutritional insult. In severe dietary restriction (fasting), a marked decrease of the number of somatogenic receptors supports the role of a receptor defect in the decline of circulating IGF-I. In contrast, in less severe forms of dietary restriction (protein restriction), the decline of IGF-I results from a postreceptor defect in the GH action at the hepatic level. Nutritional deprivation decreases hepatic IGF-I production by diminishing IGF-I gene expression. Decline in IGF-I gene expression is mainly caused by nutrient deficiency and less importantly by the nutritionally induced hormonal changes (insulin and T3). Diet restriction also increases the clearance and degradation of serum IGF-I through changes in the levels of circulating IGFBPs.(ABSTRACT TRUNCATED AT 400 WORDS)

Nutritional Regulation of the Insulin-Like Growth Factors*

Five characters separate man from other hominoids-a large neocortex, bipedality, reduced anterior dentition with molar dominance, material culture, and unique sexual and reproductive behavior. Evidence provided by the fossil record, primate behavior, and demographic analysis shows that the traditional view that early human evolution was a direct consequence of brain expansion and material culture is incorrect, and that the unique sexual and reproductive behavior of man may be the sine qua non of human origin.

https://science.sciencemag.org/content/sci/211/4480/341.full.pdf

The Origin of Man

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1990.tb15595.x

Insulin-like growth factors I and II

Seminars in medicine of the Beth Israel Deaconess Medical Center. Insulin-like growth factors.

Serum somatomedin binding proteins: physiologic significance and interference in radioligand assay.

The influence of serum triiodothyronine (T3) and thyroxine (T4) concentrations on the release of prolactin in man was studied by determining the prolactin response to synthetic thyrotropin-releasing hormone (TRH) in hypothyroid and hyperthyroid patients before and after correction of their serum thyroid hormone abnormalities. The maximum increment in serum prolactin above the basal level (maximum Δ prolactin) was used as the index of response to TRH.

In 12 patients with primary hypothyroidism, the maximum Δ prolactin in response to TRH fell from 100.5±29.1 ng/ml (mean ±SEM) before treatment to 36.1±6.0 ng/ml (P < 0.01) during the 4th wk of treatment with 30 μg T3 + 120 μg T4 daily. The mean serum T3 level increased from 57±8 to 138±10 ng/100 ml, and the mean serum T4 level increased from 3.0±0.4 to 7.2±0.4 μg/100 ml during this treatment. In eight normal subjects the maximum Δprolactin in response to TRH was not significantly different during the 4th wk of treatment with 30 μg T3 + 120 μg T4 daily from the response before treatment. In 10 patients with hyperthyroidism, the maximum Δprolactin in response to TRH increased from 14.2±2.9 ng/ml before treatment to 46.9±6.7 ng/ml (P < 0.001) during antithyroid treatment. The mean serum T3 level fell from 313±47 to 90±8 ng/100 ml, and the mean serum T4 level fell from 20.8±2.5 to 6.8±0.6 μg/100 ml during this treatment.

These results show that changes from normal serum levels of T3 and T4 are associated with changes in prolactin responses to TRH; subnormal serum levels of T3 and T4 increase TRH-induced prolactin release, whereas substantially higher than normal serum levels of T3 and T4 inhibit this release.

/pdf/thyroid-hormone-inhibition-of-the-prolactin-response-to-4uj7vr3p6u.pdf

Thyroid Hormone Inhibition of the Prolactin Response to Thyrotropin-Releasing Hormone

Diagnostic Value of Thyrotrophin-Releasing Hormone in Pituitary and Hypothalamic Diseases: Assessment of Thyrotrophin and Prolactin Secretion in 100 Patients

Induction of hypothyroidism by treatment of rats with propylthiouracil (PTU) or radioactive iodine reduced pituitary and plasma growth hormone concentrations. Radioimmunoassayable pituitary and plasma growth hormone was diminished after three weeks of PTU ingestion. By four weeks, plasma growth hormone had fallen to barely detectable levels in most animals. Pituitary growth hormone concentration reached the lowest value by 40 days and remained depressed throughout 98 days of PTU ingestion. After treatment for 21 days with PTU, rats given tap water had progressively increasing pituitary growth hormone concentrations reaching control levels within 19 days. Rats given PTU and thyroxine injections to prevent hypothyroidism had no appreciable change in pituitary or plasma growth hormone concentrations. Administration of cortisol to chronically hypothyroid animals failed to increase pituitary growth hormone content. When rats bearing the growth hormone— and prolactin— producing tumor MtTWl5 were rendered hypoth...

Alterations of Radioimmunoassayable Growth Hormone and Prolactin during Hypothyroidism

The clinical utility of synthetic thyrotrophin-releasing hormone (TRH) in assessing thyrotrophin (TSH) and prolactin secretion was evaluated in 100 patients with pituitary and hypothalamic...

William H. Daughaday

Papers

Serum somatomedin binding proteins: physiologic significance and interference in radioligand assay.

Thyroid Hormone Inhibition of the Prolactin Response to Thyrotropin-Releasing Hormone

Diagnostic Value of Thyrotrophin-Releasing Hormone in Pituitary and Hypothalamic Diseases: Assessment of Thyrotrophin and Prolactin Secretion in 100 Patients

Alterations of Radioimmunoassayable Growth Hormone and Prolactin during Hypothyroidism

Diagnostic Value of Thyrotrophin-Releasing Hormone in Pituitary and Hypothalamic Diseases