Growth hormone in the nervous system: autocrine or paracrine roles in retinal function?

2003 ◽  
Vol 81 (4) ◽  
pp. 371-384 ◽  
Author(s):  
S Harvey ◽  
M Kakebeeke ◽  
A E Murphy ◽  
E J Sanders

Growth hormone (GH) is primarily produced in the pituitary gland, although GH gene expression also occurs in the central and autonomic nervous systems. GH-immunoreactive proteins are abundant in the brain, spinal cord, and peripheral nerves. The appearance of GH in these tissues occurs prior to the ontogenic differentiation of the pituitary gland and prior to the presence of GH in systemic circulation. Neural GH is also present in neonates, juveniles, and adults and is independent of changes in pituitary GH secretion. Neural GH is therefore likely to have local roles in neural development or neural function, especially as GH receptors (GHRs) are widespread in the nervous system. In recent studies, GH mRNA and GH immunoreactive proteins have been identified in the neural retina of embryonic chicks. GH immunoreactivity is present in the optic cup of chick embryos at embryonic day (ED) 3 of the 21-d incubation period. It is widespread in the neural retina by ED 7 but also present in the nonpigmented retina, choroid, sclera, and cornea. This immunoreactivity is associated with proteins in the neural retina comparable in size with those in the adult pituitary gland, although it is primarily associated with 15–16 kDa moieties rather than with the full-length molecule of approximately 22 kDa. These small GH moieties may reflect proteolytic fragments of "monomer" GH and (or) the presence of different GH gene transcripts, since full-length and truncated GH cDNAs are present in retinal tissue extracts. The GH immunoreactivity in the retina persists throughout embryonic development but is not present in juvenile birds (after 6 weeks of age). This immunoreactivity is also associated with the presence of GH receptor (GHR) immunoreactivity and GHR mRNA in ocular tissues of chick embryos. The retina is thus an extrapituitary site of GH gene expression during early development and is probably an autocrine or paracrine site of GH action. The marked ontogenic pattern of GH immunoreactivity in the retina suggests hitherto unsuspected roles for GH in neurogenesis or ocular development.Key words: growth hormone, growth hormone receptor, nervous system, retina, autocrine, paracrine.

1993 ◽  
Vol 74 (2) ◽  
pp. 225-233 ◽  
Author(s):  
Peter E. Lobie ◽  
Juanita García-Aragón ◽  
David T. Lincoln ◽  
Ross Barnard ◽  
Josiah N. Wilcox ◽  
...  

1992 ◽  
Vol 12 (6) ◽  
pp. 2624-2632
Author(s):  
D Murphy ◽  
K Pardy ◽  
V Seah ◽  
D Carter

In thyroid hormone-depleted rats, the rate of transcription of the growth hormone (GH) gene in the anterior pituitary gland is lower than the rate in euthyroid controls, and there is a corresponding reduction in the abundance of the GH mRNA. Concomitantly, the poly(A) tail of the GH mRNA increases in length. Examination of nuclear RNA from anterior pituitary glands of control and thyroid hormone-depleted rats revealed no difference in the length of pre-mRNAs containing the first and last introns of the GH gene. However, mature nuclear GH RNA is differentially polyadenylated in euthyroid and hypothyroid animals. We suggest that the extent of polyadenylation of the GH transcript is regulated in the cell nucleus concomitant with or subsequent to the splicing of the pre-mRNA. Experiments with anterior pituitary gland explant cultures demonstrated that the GH mRNA from thyroid hormone-depleted rats is more stable than its euthyroid counterpart and that the poly(A) tail may contribute to the differential stability of free GH ribonucleoproteins.


2021 ◽  
Vol 7 (27) ◽  
pp. eabh3805
Author(s):  
Noah Kassem ◽  
Raul Araya-Secchi ◽  
Katrine Bugge ◽  
Abigail Barclay ◽  
Helena Steinocher ◽  
...  

Because of its small size (70 kilodalton) and large content of structural disorder (>50%), the human growth hormone receptor (hGHR) falls between the cracks of conventional high-resolution structural biology methods. Here, we study the structure of the full-length hGHR in nanodiscs with small-angle x-ray scattering (SAXS) as the foundation. We develop an approach that combines SAXS, x-ray diffraction, and NMR spectroscopy data obtained on individual domains and integrate these through molecular dynamics simulations to interpret SAXS data on the full-length hGHR in nanodiscs. The hGHR domains reorient freely, resulting in a broad structural ensemble, emphasizing the need to take an ensemble view on signaling of relevance to disease states. The structure provides the first experimental model of any full-length cytokine receptor in a lipid membrane and exemplifies how integrating experimental data from several techniques computationally may access structures of membrane proteins with long, disordered regions, a widespread phenomenon in biology.


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