Subject Index Acromegaly, somatostatin analog therapy dopamine agonist combination therapy 132 efficacy 132, 133 overview 130, 131 receptor subtype response 131, 132 SOM30 studies 131, 132 ACTH, see Adrenocorticotropic hormone Adrenocorticotropic hormone (ACTH), see also Cushing disease ectopic secretion, see Ectopic adrenocorticotropin secretion isolated deficiency 81, 82 processing 158 secretion regulation 158, 159 Angiogenesis, see Vascular endothelial growth factor Vasoinhibins Anterior pituitary cell renewal circadian rhythm 10 estrous cycle apoptosis regulation 13 15, 17, 18 cell proliferation 10 13 estrogen modulation 11 13, 15, 17 overview 10 progesterone effects 17 Arginine vasopressin (AVP) gene therapy in Brattleboro rat 136, 137 158 Atherosclerosis, ghrelin role 108 110 AVP, see Arginine vasopressin Bilateral inferior petrosal sinus sampling (BIPSS) Cushing disease diagnosis 173 BIPSS, see Bilateral inferior petrosal sinus sampling BMPs, see Bone morphogenetic proteins Bone morphogenetic proteins (BMPs) BMP-4 adult pituitary cell expression and effects 25 functional overview 24 prolactinoma role 25, 26, 28 retinoic acid effect mediation in corticotropes 27 pituitary development role 24, 25 signaling 23, 24 transforming growth factor- superfamily 22, 23 Computed tomography (CT), adrenocorticotropin-secreting tumors 149, 150 Corticotrope bone morphogenetic protein-4 inhibitory effects 27 retinoic acid effect mediation 27 differentiation regulation 80, 81 Corticotropin-releasing hormone (CRH) 158 testing 180
Cushing disease 172 CRH, see Corticotropin-releasing hormone CT, see Computed tomography Cushing disease, see also Ectopic adrenocorticotropin secretion clinical manifestations 170, 171 diagnosis 171 differential diagnosis 172, 173 management dopamine agonists 174 peroxisome proliferator-activated receptor- ligands 176, 177 retinoic acid 175, 176 somatostatin analogs 174, 175 Dexamethasone suppression test Cushing disease diagnosis 171 Dopamine agonists acromegaly management 132 Cushing disease management 174 prolactinoma management algorithm 89 efficacy 88, 95 98 long-term follow-up macroadenoma patient groups 91, 92 microadenoma patient groups 90, 91 study design 90 prognostic factors 95 98 withdrawal studies 93 95 Dopamine D2 receptor gene structure 52 knockout mouse cell adhesion in tumorigenesis 59 phenotype 52, 53 prolactinoma model 52 sex-dependent pituitary hyperplasia 54 vascular endothelial growth factor-a modulation of pituitary hyperplasia angiogenesis induction 54, 55, 58, 59 cell distribution 56, 57 expression 56 peliosis role 57, 58 prolactin-releasing effect 58 therapeutic targeting 60 receptor classification 51 tissue distribution 51, 52 transforming growth factor- type II receptor interactions in prolactinoma 42, 43 EAS, see Ectopic adrenocorticotropin secretion Ectopic adrenocorticotropin secretion (EAS) adrenocorticotropin hormone sources 144, 145 clinical presentation 145, 146 Cushing syndrome differential diagnosis 143, 144, 147 diagnosis 146 149 management 150 153 tumor localization 149, 150 EGF, see Epidermal growth factor Epidermal growth factor (EGF) Estrogen anterior pituitary cell renewal modulation in 13, 15, 17 growth hormone interactions formulations and administration route effects 116, 117, 119 considerations 119 122, 125, 126 puberty in females 116 effects aging studies 162, 163, 166 forebrain cholinergic system mediation of hippocampal effects hippocampal neurogenesis role 164, 165 neuroendocrine effects 161, 162 prolactinoma induction studies dopamine D2 receptor interaction with transforming growth factor- type II receptor 42, 43 folliculo-stellate cell communication with lactotropes 39, 40 Subject Index 181
Estrogen (continued) prolactinoma induction studies (continued) gap-junctional communication 40 mitogen-activated protein kinase signaling 40, 41, 44 mitogenic factors 35, 36 rat model 33, 34 transforming growth factor- isoforms in cell growth balance 37 39 xenoestrogen studies 36, 37 receptor isoforms 161 Estrous cycle, anterior pituitary cell renewal apoptosis regulation 13 15, 17, 18 cell proliferation 10 13 estrogen modulation 11 13, 15, 17 overview 10 progesterone effects 17 FGFs, see Fibroblast growth factors Fibroblast growth factors (FGFs) FGF-8 and pituitary development role 25 Gene therapy hypothalamus aging female rat studies 137, 138 Brattleboro rat 136, 137 leptin receptor mutant rat studies 137 overview 135, 136 Parkinson disease prospects 140 pituitary gland retinoblastoma mutant mouse 139, 140 suicide gene therapy in tumors 140 GH, see Growth hormone Ghrelin adipocyte function 108 atherosclerosis role 108 110 functions 102, 103, 110, 111 pancreas expression and function 105 107 receptors knockout mouse phenotype 103 tissue distribution 104, 105 types 102, 103 secretion regulation 103, 104 Glucocorticoids inhibitory feedback control 159 161 post-traumatic stress disorder role 160 Gonadotrope, differentiation regulation 79, 80 Growth hormone (GH) economics of replacement therapy 125, 126 estrogen effects formulations and administration route effects 116, 117, 119 considerations 119 122, 125, 126 puberty in females 116 excess, see Acromegaly insulin interactions 116 somatostatin regulation 125 testosterone interactions energy and protein metabolism effects 122 124 considerations 125, 126 overview 122 Gs, mutation in pituitary adenoma 2 Hesx1 pituitary formation role 76, 77 Hippocampus, estrogen effects forebrain cholinergic system mediation neurogenesis role 164, 165 HPA axis, see Hypothalamic-pituitaryadrenal axis Hypothalamic-pituitary-adrenal (HPA) axis estrogen effects aging studies 162, 163, 166 forebrain cholinergic system mediation of hippocampal effects hippocampal neurogenesis role 164, 165 neuroendocrine effects 161, 162 functional overview 157 159 steroid inhibitory feedback control 159 161 Subject Index 182
IGFs, see Insulin-like growth factors Insulin, growth hormone interactions 116 Insulin-like growth factors (IGFs) gene therapy 138, 139 Insulin resistance, ghrelin role 106, 107 Ketoconazole, ectopic adrenocorticotropin secretion management 151 Lhx3 Lhx4 Magnetic resonance imaging (MRI) adrenocorticotropin-secreting tumors 149, 150 pituitary 172, 173 MAPK, see Mitogen-activated protein kinase Melanotrope, differentiation regulation 80, 81 Metyrapone, ectopic adrenocorticotropin secretion management 151 Mitogen-activated protein kinase (MAPK), estrogen signaling in prolactinoma 40, 41, 44 MRI, see Magnetic resonance imaging Nitric oxide (NO), vasoinhibin effects on production 67, 68 NO, see Nitric oxide PDGF, see Platelet-derived growth factor Peroxisome proliferator-activated receptor- (PPAR- ), ligands in Cushing disease management 176, 177 Pituitary adenoma, see also specific tumors epidemiology 32 gene mutations 2, 3 PTTG transgenic mouse studies 4 6 suicide gene therapy in tumors 140 tropic status as modulator of tumor formation 2 4 Pitx1 pituitary cell lineages 78, 79 Pitx2 Platelet-derived growth factor (PDGF), PPAR-, see Peroxisome proliferatoractivated receptor- Prolactinoma angiogenesis 60, 61 animal models aging rodents 33 alcohol-treated rat 34 36 dopamine D2 receptor knockout mouse, see Dopamine D2 receptor estrogen-treated rat 33, 34 overview 50, 51 bone morphogenetic protein-4 role 25, 26, 28 clinical manifestations 33 dopamine agonist therapy algorithm 89 efficacy 88, 95 98 long-term follow-up macroadenoma patient groups 91, 92 microadenoma patient groups 90, 91 study design 90 prognostic factors 95 98 withdrawal studies 93 95 epidemiology 32, 59 estrogen induction studies dopamine D2 receptor interaction with transforming growth factor- type II receptor 42, 43 folliculo-stellate cell communication with lactotropes 39, 40 gap-junctional communication 40 mitogen-activated protein kinase signaling 40, 41, 44 Subject Index 183
Prolactinoma (continued) estrogen induction studies (continued) mitogenic factors 35, 36 transforming growth factor- isoforms in cell growth balance 37 39 xenoestrogen studies 36, 37 menopause effects 96, 97 pregnancy effects 96 spontaneous regression 96 Prop1 pituitary formation role 76, 77 PTTG, pituitary adenoma role defects 3, 4 transgenic mouse studies 4 6 Rathke s pouch, formation 74, 75 Rb, see Retinoblastoma protein Retinoblastoma protein (Rb), gene therapy 139, 140 Retinoic acid bone morphogenetic protein-4 mediation in corticotropes 27 Cushing disease management 175, 176 SCLC, see Small cell lung cancer Small cell lung cancer (SCLC), ectopic adrenocorticotropin secretion 144 146, 149 SOM30, acromegaly studies 131, 132 Somatostatin receptor growth hormone secretion regulation 129 signaling 130 somatostatin analogs acromegaly management dopamine agonist combination therapy 132 efficacy 132, 133 overview 130, 131 receptor subtype response 131, 132 SOM30 studies 131, 132 binding 129, 130 Cushing disease management 174, 175 development 131 stability 130 subtypes 129, 130 Testosterone, growth hormone interactions energy and protein metabolism effects 122 124 considerations 125, 126 overview 122 TGF-, see Transforming growth factor- TNF-, see Tumor necrosis factor- TPIT, proopiomelanocortin-expressing cell differentiation role 80, 81 Transforming growth factor- (TGF- ) lactotrope isoforms in cell growth balance 37 39 mitogenesis 35 type II receptor interactions with dopamine D2 receptor in prolactinoma 42, 43 Tumor necrosis factor- (TNF- ), apoptosis regulation in anterior pituitary 13, 15, 17, 18 Vascular endothelial growth factor (VEGF), VEGF-A and pituitary hyperplasia modulation in dopamine D2 receptor knockout mouse angiogenesis induction 54, 55, 58, 59 cell distribution 56, 57 expression 56 peliosis role 57, 58 prolactin-releasing effect 58 therapeutic targeting 60 Vasoinhibins angiogenesis inhibition mechanisms 67, 68 eye angiogenesis studies 68, 69 pituitary distribution and function 69, 70 processing from prolactin 66 types 66, 67 VEGF, see Vascular endothelial growth factor Subject Index 184