vasoactive-intestinal-peptide and Growth-Disorders

Adult growth hormone deficient patients are known to exhibit reduced sweating and their ability to thermoregulate is diminished. Treatment of these patients with recombinant human growth hormone (r-hGH) is claimed to reverse these abnormalities. We have investigated this claim, as well as the mechanism underlying these altered sweating responses in GH-deficient patients as part of a placebo-controlled study on the effects of 6-12 months r-hGH therapy. Skin biopsies were obtained from these subjects and changes in morphology and innervation parameters for the eccrine sweat glands were examined. These included histochemistry for acetylcholinesterase (AChE) and immunohistochemistry for the neuropeptide vasoactive intestinal polypeptide (VIP) and for PGP9.5, a general neuronal marker. Sweat gland acinar size and periacinar innervation were measured by computerised image analysis. The patients underwent pilocarpine iontophoresis sweat rate tests and their serum insulin-like growth factor 1 (IGF-1) levels were assessed. Since active acromegaly involves excess GH secretion and hyperhidrosis, skin biopsies and sweat tests were also carried out on a group of these patients, as well as on control subjects. We have demonstrated a sweating defect in adult GH-deficiency which is accompanied by a reduction in AChE and VIP levels in the nerve supply to sweat glands. Following r-hGH therapy, an increase in AChE and VIP staining is seen in the sudomotor nerves accompanied by restoration of sweat rates and serum IGF-1 levels. Hence, normalization of sweat gland function includes recovery of sudomotor synapse constituents. A trophic effect of GH on sweat gland epithelium and/or on the associated nerves is proposed, supported by the observation that in acromegaly the size of sweat gland acini and the density of innervation to the sweat glands was greater than in controls.

Topics: Acetylcholinesterase; Acromegaly; Adult; Antigens, Differentiation; Biopsy; Female; Growth Disorders; Growth Hormone; Human Growth Hormone; Humans; In Vitro Techniques; Insulin-Like Growth Factor I; Iontophoresis; Male; Middle Aged; Muscarinic Agonists; Pilocarpine; Sweat Glands; Sweating; Sympathetic Nervous System; Thyroxine; Triiodothyronine; Tyrosine 3-Monooxygenase; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

Pituitary adenylyl cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two closely related neuropeptides exhibiting overlapping activities which have actions on almost every organ system of the body. To determine if these peptides exert essential but redundant functions, we interbred VIP- and PACAP-deficient mice to obtain VIP/PACAP double knockout (DKO) mice. DKO mice had normal birth weights and survived to weaning, but exhibited a dramatic postnatal growth rate reduction. Analyses at postnatal day 16 indicated that all organs examined except the brain were reduced in mass by 40-70% compared to mixed background controls, with the thymus and spleen most profoundly affected. Brain size was also significantly reduced, but by only 10%. The reduced growth rate of DKO mice was associated with reduced serum concentrations of insulin-like growth hormone-1 (IGF-1), but unchanged levels of growth hormone. Despite the normal survival of DKO mice up to the weaning stage, many subsequently experienced early sudden death, with only 48% of females and 82% of males surviving past 6 months. The results indicate that a significant percentage of mice deficient in both VIP and PACAP survive to adulthood, but their growth rate is profoundly affected, and that females in particular exhibit high rate of mortality after about 3 months of age.

Topics: Animals; Female; Growth Disorders; Growth Hormone; Male; Mice; Mice, Knockout; Phenotype; Pituitary Adenylate Cyclase-Activating Polypeptide; Somatomedins; Survival Rate; Vasoactive Intestinal Peptide

Topics: Adrenal Gland Neoplasms; Child; Diagnosis, Differential; Diarrhea; Female; Ganglioneuroma; Growth Disorders; Humans; Male; Vasoactive Intestinal Peptide