I= THE ROLE OF EXCITATORY AMINO ACID NEUROTRANSMITTERS IN THE CENTRAL REGULATION OF GROWTH HORMONE SECRETION IN NONHUMAN PRIMATES
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Title of Thesis
THE ROLE OF EXCITATORY AMINO ACID NEUROTRANSMITTERS IN THE CENTRAL REGULATION OF GROWTH HORMONE SECRETION IN NONHUMAN PRIMATES

Author(s)
Saima Huma
Institute/University/Department Details
Department of Biological Sciences/ Quaid-i-Azam University, Islamabad
Session
2005
Subject
Biological Sciences
Number of Pages
174
Keywords (Extracted from title, table of contents and abstract of thesis)
excitatory amino acid neurotransmitters, growth hormone secretion, nonhuman primates, somatotropic cells, macaca mulatta, insulin treatment, bolus

Abstract
GH is a multifunctional protein hormone with a polymorphic nature. It is well recognized for its action to promote growth of skeletal and soft tissues as well as its effects on metabolism. GH is synthesized in somatotropic cells in the anterior pituitary and release into the circulation to reach its target organs in the body. The secretion of GH is controlled by hypothalamic peptides. The release of the hormone is thus stimulated by a GH releasing factor (GRF) and inhibited by somatostatin. In mammals GH is secreted episodically, which is essential for optimal growth, and a distinct male and female secretory pattern.

Monkeys were housed in individual cages and were maintained under standard colony conditions. The animals were provided with standard monkey food supplemented with fresh fruits and vegetables. Water was available ad labitum. The animals were chair restrained daily for about four hours for a period of twenty days. The animals were anaesthetized with Ketamine hydrochloride and while under sedation two tephlon cannulae were inserted in the sphanous vein for blood sampling and drug infusion. Sequential blood samples were collected at 15 min interval in heparinized syringes. Following withdrawal of each sample, an equal volume of heparinized (5 IU/ML) saline was injected into the tubing. Blood samples were centrifuged immediately at 3000 rpm for 10 min. Plasma was separated and stored at -150C until analyzed. Plasma levels of GH were determined in duplicate using human Double Antibody Radio Immunoassay (RIA) Kit.

The present study was designed to investigate the involvement of excitatory amino acid neurotransmitters (EAA) in the regulation of basal/stimulated GH secretion in rhesus monkeys (Macaca mulatta). Four sets of experiments were performed. In the first set of experiment (control experiment) saline injection was given at 0 min to all the four monkeys. In the second set of experiments, a single injection of Mk-801 (0.1 mglkg, BW, dissolved in 5 ml saline) was administered at 0 min in all the four monkeys. In the third sets of experiments insulin bolus injection (1.0 unit/kg= 25 Dl/kg) was given to all the animals. While in the fourth sets of experiments the animals were administered an injection of insulin immediately following by an injection of MK-801. Results showed that Saline infusion caused no significant change in basal plasma OH concentrations. While administration of MK-801 decreased plasma OH concentrations significantly (p<0.001) over the basal levels. Likewise insulin treatment (bolus) significantly (p<0.001) increased the OH profile. While insulin when given in combination with MK801 significantly (p<0.001) increased plasma OH concentrations.

In order to investigate the interaction of excitatory amino acid neurotransmitters (EAA) with cholinergic pathway in the regulation of OH secretion four sets of experiments were performed. In the first set of experiment (control experiment) saline injection was given at 0 min to all the animals. In the second set of experiments, a single injection of NMA (15 mg/kg, BW, dissolved in 5 ml saline) was administered at 0 min. In the third sets of experiments atropine bolus (5 mg dissolved in 5 ml saline) injection was given to all the monkeys. While in the fourth sets of experiments the animals were challenged with a single injection of NMA at 30 min after pretreatment of atropine bolus at 0 min. Results showed that Saline infusion caused no significant(p>0.05) change in basal plasma OH concentrations. While administration of NMA increased plasma OH concentrations significantly (p

To elucidate the interaction of excitatory amino acid neurotransmitters (EAA) with opioid pathway in the regulation of OH secretion four sets of experiments were performed. In the first set of experiment (control experiment) saline infusion (6 ml/2hr) was given through a pump at the rate of 3 ml/hr for two hrs to all the four monkeys. In the second set of experiments, two NMA injections (15 mg/kg, BW, dissolved in 10 ml saline) were administered at 30 and 60 min respectively. In the third sets of experiments NX bolus (5mg/animal dissolved in 5 ml saline) alongwith infusion (1.5 mg/kg/hr at the rate of 3ml/hr) was given for a period of 3 hrs. While in the fourth sets of experiments the animals were challenged with two injections of NMA at 30 and 90 min respectively during NX bolus plus infusion treatment. Results showed that Saline infusion caused no significant change in basal plasma GH concentrations. While administration of both the NMA injections increased plasma GH concentrations significantly (p<0.001) over the basal levels. Likewise NX treatment (bolus plus infusion) significantly (p<0.001) reduced the GH profile. While NMA when administered during pretreatment of NX significantly (p<0.001) increased GH levels.

To investigate the interaction of excitatory amino acid neurotransmitters (EAA) with a-adrenergic pathway in the regulation of GH secretion four sets of experiments were performed. In the first set of experiment (control experiment) saline infusion (6 ml/2hr) was given through a pump at the rate of 3 ml/hr for two hrs to all the four monkeys. In the second set of experiments, two NMA injections (15 mg/kg, BW, dissolved in 10 ml saline) were administered at 30 and 90 min respectively. In the third sets of experiments Phantolamine bolus (5mglanimal dissolved in 5 ml saline) alongwith infusion (1.5 mg/kglhr at the rate of 3ml/hr) was given for a period of 4 hrs. While in the fourth sets of experiments the animals were challenged with two injections of NMA at 60 and 120 min respectively during Phantolamine bolus plus infusion treatment. Results showed that Saline infusion caused no significant change in basal plasma GH concentrations. While administration of both the NMA injections increased plasma GH concentrations significantly (p<0.001) over the basal levels. Phantolamine treatment (bolus plus infusion) significantly (p<0.001) reduced the GH profile. While NMA when administered during pretreatment of Phantolamine failed to produce any effect and plasma GH profile remained significantly (p<0.01) low even after NMA administration.

In conclusion present study suggests that endogenous excitatory amino acids may be involved in the regulation of basal GH secretions but insulin-stimulated GH secretions may not be regulated by excitatory amino acids. Secondly, cholinergic and opioid pathways may be involved in the regulation of basal GH secretions but NMA-stimulated GH release may not be mediated through these two pathways. Finally, O-adrenergic pathways are involved not only in the regulation of basal GH secretions but NMA stimulated-GH release may also be regulated through this pathway.

Download Full Thesis
19300.32 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
3496.38 KB
2 1 Involvement Of Endogenous Excitatory Amino Acid Neurotransmitters In The Regulation Of Basal / Stimulated Growth Hormone Secretion
3173.15 KB
3 2 Interaction Of Excitatory Amino Acid Neurotransmitters With Cholinergic P A Thw A Y In The Regulation Of Growth Hormone Secretion
2353.19 KB
4 3 Interaction Of Excitatory Amino Acid Neurotransmitters With Opioid Path Way In The Regulation Of Growth Hormone Secretion
3035.23 KB
5 4 Interaction Of Excitatory Amino Acid Neurotransmitters With Adrenergic Pathway In The Regulation Of Growth Hormone Secretion
1632.67 KB
6 5 General Discussion
192.33 KB
  5.1 References