Gonadotropin-releasing hormone and its receptor in normal and malignant cells
- 1University of Colorado Health Sciences, Department of Medicine, 4200 East Ninth Avenue, Denver, Colorado 80262, USA
- 2Veterans Affairs Medical Center, Denver, Colorado 80220, USA
- 3Colorado State University, Department of Physiology, Animal Reproduction and Biotechnology Laboratory, Fort Collins, Colorado 80523, USA
- (Requests for offprints should be addressed to L M Glode; Email: mike.glode{at}uchsc.edu)
-
Figure 1
The hypothalamic–pituitary–gonadal axis. Secretion of GnRH from the hypothalamus occurs in a pulsatile fashion and is partially responsible for controlling the number of GnRHRs in the pituitary gland and controls synthesis and secretion of FSH and LH. These gonadotropins in turn regulate function of the testes and ovaries. E, estrogen; P, progesterone; T, testosterone.
-
Figure 2
Effects of GnRH activation of its receptor in stimulating diverse signaling pathways in the anterior pituitary. (Reprinted with permission from Ruf et al. (2003)).
-
Figure 3
Median (±s.e.m.) serum testosterone level in patients treated with abarelix depot (broken line) and those treated with leuprolide acetate and bicalutamide (solid line) on study days 1 through 169. (Reprinted with permission from Trachtenberg et al. (2002)).
-
Figure 4
Eastern Cooperative Oncology Group: disease-free and overall survival data. Kaplan–Meier estimates of overall survival and disease-free survival in patients receiving immediate versus deferred hormonal therapy. (From Crawford (2003), adapted with permission from Messing et al.(1999)).
-
Figure 5
Mechanism by which hormonotoxins may lead to cell death. The ligand–toxin conjugate binds to specific receptors on the surface of target cells (1) and is then internalized via receptor-mediated endocytosis (2). Once inside the cell, the conjugate (or the toxin alone) enters the cytoplasm by an unknown mechanism (3) and inhibits protein synthesis; the mechanism by which this occurs depends on the type of toxin. Pseudomonas exotoxin (PE) and diphtheria toxin (DT) inactivate elongation factor-2 (EF-2), whereas plant toxins (ricin toxin A (RTA); ribosome-inactivating protein (RIP)) inactivate 28S RNA. In either case, the intoxicated cell is unable to synthesize proteins which results in cell death. (Adapted with permission from Thrush et al. (1996)).
-
Figure 6
Clonogenic assay in (A) CHO-GnRHR or (B) CHO control cells exposed to varying concentrations of PAP, GnRH–mPAP fusion protein or GnRH–PAP conjugate. Values are means±s.e.m. (Reprinted with permission from Qi et al. 2004).
-
Figure 7
Effects (means±s.e.m.) of GnRH–toxin or toxin alone on the ability of cultured anterior pituitary cells to synthesize LH (solid bars) or prolactin (shaded bars). Toxin alone did not alter LH synthesis compared with untreated cells, but GnRH–toxin substantially decreased (P < 0.01) synthesis of LH. In contrast, GnRH–toxin did not influence the ability of cultured pituitary cells to synthesize prolactin (P > 0.05).
-
Figure 8
Cytotoxicity of GnRH–PAP conjugate against (A) CHO-GnRHR and (B) αT3-1 cells in the cell proliferation assay, with various concentrations of GnRH–PAP (•), d-Lys6-GnRH (▴) or PAP (▪). Values are means±s.e.m. (Reprinted with pemission from Yang et al. (2003)).
-
Figure 9
Effects (means±s.e.m.) of GnRH–PAP on reproductive parameters in male dogs. Treatment regimens are described in the text. Arrows in (A) indicate the times that treatments were administered. (A) Changes in serum concentrations of testosterone at various times after treatments. The ability of the anterior pituitary to respond to a GnRH challenge is shown in (B); data shown represent the total amount of LH released (AUC) following the challenge. Changes in testicular volume with time after treatments is depicted in (C). Since each of the treatment regimens resulted in decreased testicular volume, data from all the treatment groups were combined. (Reprinted with pemission from Sabeur et al. 2003)).
- © 2004 Society for Endocrinology
