INDEX

ACTH Aromatase in tetrahymena pyriformis, 76 activity, 469 Adenylate Cyclase Armatase activity inhibition by somatostatin, granulosa cells, 317 377 OS induced, 253 Administered LHRHA with testosterone enanthate, 598 Bacteria Adrenal androgens binding of TSH, 77 in prostatic cancer, 540 Blocking agents Agonist or antagonist of receptor, 222 binding to receptor, 242 Ca2+ Androgen insensitive cells interaction of receptor, 267 exposed to low androgen, 542 on intracellular events, 267 Androgen receptor blockers Calmodulin inhibitors cyproterone acetate, flutamide, block GnRH, 160 558 cAMP Angiotensin 11 activation of phospho• PRL release, 359, 361 diesterase, 413 function cumulus-oocyte complex, 328 neuromodulators, 48 regulation of oocyte Antral f1uid maturation, 326 FSH, LH and prolactin, 320 cAMP accumulation steroid hormone concentrations, LH-induced, 333 319 oocyte maturation, 332 AP cells cAMP and 20a-OH-P information on membrane compart• response to OS or FSH, 257 ments, 170 cAMP binding activity Arachidonic acid effects of FSH and LHRH, 473 action of LHRH, 6 cAMP levels Arachidonic acid (AA) pregnenolone production, 429 prostaglandins (PG), 494 cAMP phosphodieste~se Arachidonic acid conversion stimulated by Ca ,calmodulin, preovulatory follicles, 348 414 Arachidonic acid metabolites Casein secretion of LH, 6 encoded by complex split genes, Arachodonic metabolites 389 in ovulation, 344 gene structure, 389

611 612 INDEX

6 Casein mRNAs D-Arg analog sequences, 389 of LH-RH, 522 a-casein Deglycosylated phosphorylation site, 391 acute effects, 227 y-casein gene antagonists, 608 hormone binding sites, 392 desentization, 241 structure, 390 preparation, 224 Cell response regulation Demorphin phosphodiesterase, 417 LH, FSH secretion, 40 Cholesterol prolactin release, 43 for steroidogenic tissues, 292 Desensitization Cholesterol availability hormone-induced, 243 uptake of lipoproteins, 424 hormone-receptor complexes, 236 Cholesterol side-chain cleavage DG-gonadotropins regulation, 426 antagonistic activity, 229 Chromatography DGhCG and hCG degradation products of LHRH, cycSic AMP response, 239 119 D-Lys -GnRH CL function agonist dimer, 159 controlled by PRL, LH and immobile support, 154 placental lactogen, 291 Dopamine Collagen degradation release of LHRH, 7 cysteine, 342 Dopamine agonists Collagen degrading enzymes anterior pituitary cells, 375 follicular rupture, 338 Down regulation Copper continuous high concentrations regulation of LHRH release, LHRH, 608 35 low concentrations LHRH, 608 Corpora lutea up-regulation, 608 in culture, 281 estradiol treatment, 278 in organ culture, 278 E pr~.freatment progesterone and 20-dihydro- Ca -dependent protein phosphory• progesterone, 279 lation, 301 Endocrine and nervous system dependence of estradiol, 276 boundaries, 73 functional regulation, 264 a-endorphin antiserum regression, 268 elevated plasma LH, 511 Covalent linking Ergot alkaloids of photoreactive GnRH, 131 adenylate cyclase receptor, 374 Cumulus cells Estradiol uridine uptake, 334 inhibition of translation, 405 Cyclic AMP formation on luteal steroidogenesis, 296 effect of DGFSH and DghCG, 242 l7a estradiol Cycling female rats luteotrophic hormone, 274 serial fields, 186 luteotrophic hormone in rabbit, 28~ Cysteine Estradiol implant prevented ovulation, 340 serum progesterone, 277 Estradiol-treated rabbits progesterone, 275 INDEX 613

Estrogen FSH release luteal weight, 291 prostacyclin, 12 Estrogens FSH cell population cardiovascular side-effects, proestrous females, 193 542 FSHRF Estrous cycle activity of FSH, 20 adenohypophyseal muscarinic receptors, 57 Gene expression milk protein, 386 Flutamide GH3 cells antiandrogen, 541 secretory activity, 174 Follicle visualized, 172 dominant, 476 GnRH healthy and atretic, 310 antiserum treatment, 146 numbers of granulosa cells, binding by the receptor, 153 314 calmodulin, 160 microenvironment, 310 clinical applications, 564 morphologic and hormonal desensitization, 160 characterization, 312 fluorescent analogs, 154 peptide hormones, 318 gonadotroph differentiation, 147 progesterone/estradiol ratio, induction of ovulation, 566 321 internalization, 134 proteins in regulation, 476 mode of action, 563 Follicle-enclosed oocytes PA and P1 labeling, 497 maturation, 331 phospholipid in interstitial Follicular cAMP levels cells, 502 oocyte maturation, 331 phospholipid labeling in , Follicular cells 502 Gap junctions, 201 photoaffinity derivative, 128 Follicular rupture pulsatile administration, 586, 537 arachidonic acid, 345 pulsatile induction of ovulation, collagenolysis, 338 576 lipoxygenase, 349 pulsatile therapy, 564 lipoxygenase products, 346 response system, 157 plasminogen activator, 341 rhodamine derivative, 133 proteolytic activity, 337 testicular P1 labeling, 500 Forskolin GnRHa cAMP response, 328 labeling of phospholipids, 499 cumulis-enclosed oocytes, 330 GnRH agonists FSH calcium dependent, 503 gastric inhibitory peptide, 16 no effect on cAMP, 501 separate hypothalamic control, granulosa and luteal cells, 202 19 GnRH and analogs FSHS structures, 128 l5-base oligomer, 402 GnRH and LH FSH and LH release stimulation 9f ovarian functions, effects of various peptides, 18 504 614 INDEX

GnRH antagonist Gonadotropes (continued) desensitization, 161 LH and FSH types, 181 molecules crosslinked, 158 monohormonal and multihormonal, GnRH-like substances 188 produced by the , 505 volume and area, 185 GnRH molecule Gonadotrope population binding affinity, 163 in adult female rat, 191 conformational analysis, 163 Gonadotrope responses GnRH occupancy requirements of, 163 receptor numbers, 161 Gonadotropic cell GnRH-R Golgi zone, 176 post-castration fall, 145 Gonadotrophic hormones GnRH recentor ovarian function, 200 down-regulation, 144 Gonadotroph microaggregation, 164 cAMP, 5 modulation of numbers, 208 cAMP, 5 in pituitary gonadotrophs, 210 control by peptides, 3 in suckling, 146 Gonadotrophs GnRH recep tors interaction with lactotrophs, correlation with GnRH secretion, 360 142 lactotroph junctional complexes, distribution, 132 355 identification, 129 many are monohormonal, 608 induce GnRH-R, 143 PRL-releasing activity, 362 physiological regulation, 142 signal to lactotrophs, 357 GnRH-receptor complex Gonadotroph-lactotroph intracellular compartments, 154 interactions, 362 GnRH-stimulated Gonadotropins gonadotropin release, 497 deglycosylated, 206 GnRH stimulation test deglycosylated derivatives, 235 anovulatory, amenorrheic women, removal of sugar residues, 223 565 resumption of meiosis, 325 GnRH target organs selective hypothalmic control, phospholipid labeling, 497 9-10 GnRH therapy strategies for inhibition, 220 in luteal phase deficiency, 571 Gonadotropin antagonists Golgi membrane antigen properties, 232 subcellular localization, 177 Gonadotropin function Golgi zone pulsatile administration of intracisternal transit of Gn-RH, 584 hormones, 170 Gonadotropin receptor Gonadectomy blocking agents, 221 increases synthesis of subunits, hormonal complex localization, 406 200 synthesis, release of gonado• modified gonadotropin, 223 tropins, 400 Gonadotropin release Gonadotropes catecholamines, 10 in cell population, 184 Gonadotropin-releasing activity GnRH stimulated, 190 vertebrate LH-RHs, 445 INDEX 615

Gonadotropin secretion hCG antagonist acetylcholine, 13 termination of pregnancy, 231 cholecystokinin, 15 hCG and DG-hCG estrogen, 4 interstitial cells, 228 frequency modulated by LHRH, HDL and hCG binding 552 luteal cells, 299 neurotensin and gastrin, 15 HMC-CoA reductase how opiotes inhibit, 516 effect of estradiol and testos• progesterone, 4 terone, 302 pulsatile pattern, 578 Hormone molecules role of the hypothalmaus, 584 gone astray, 73 substance P, 15 Hormone-receptor testosterone, 4 internalized, 204 VIP, 15 Hormone-receptor complexes Gonadotropin storage processing, 134 analysis of, 188 Hormonal regulation estrous cycle, 187 casein gene family, 392 Gonadotropin subunits Hormonal release mechanisms estradiol, 398, 400 multireceptor regulation, 56 synthesized as precursors, 406 Hormone storage Gonadotropin subunit precursor gonadotropes, 184 gonadectomy, 398 Hormones Gonadotropin synthesis in antral fluid, 312 effect of LHRH, 96 in follicle, 310 Granulosa Hormones in antral fluid steroid products, 471 functional correlates, 316 Granulosa cells Hybridization aromatase activity, 468 specific mRNAs, 404 cholesterol side-chain cleavage, Hypothalamic amenorrhea 470 gonadotropin secretion, 579 culture techniques, 249 grading, 580 OS morphological changes, 251 pituitary responses to Gn-RH, progesterone, 472 583 differentiation pulsatle Gn-RH, 585 mechanism, 201 reduced Gn-RH, 584 Granulosa cell phosphodiesterase suprapituitary origin, 579 FSH regulation, 416 Hypothalamic factors Granulosa cell structure modulating prolactin, 367 degradation of hCG, 240 Hypothalamic granules GTP effect incubated with CuHistadine or binding somatostatin, 376 CuCysteine, 33 Hypothalamic implants into hpg mice, 148 hCG Hypothalamic mRNA arachidonic acid conversion, 349 translation products, 91, 93 luteal cell, 294 Hypothalamic-pituitary system in nuclear fractions, 204 main features, 606 ovarian secretion, 293 synthesis of T and E, 294 616 INDEX

Insulin LH action in tetrahymena, 74 on prognenolone production, 426 Infertle women LH and FSH release clinical characteristics, 568 prolonged suppression, 523 results of GnRH therapy, 570 LH and GnRH Immunological probes increase PGE production, 503 membrane antigens, 178 LH and GnRHa secretory protein (PRL), 178 indomethacin blocked, 503 Intercellular communication LH and LHRH concepts, 72 different mechanisms, 489 Internalization LH and LHRHa effects trophic effects of hormone, calcium dependency, 432 211 LH binding Intracellular transit site of, 201 secretory proteins, 71 LH cells during estrous, 193 LH concentrations Lactation isoproterenol, 9 progesterone, 387 propalolol, 9 Lactotrophs LH in plasma integration of information, effects of S-endorphin antiserum, 369 512 Lactotrophs LH pulses TRH, 359 hypothalamic amenorrhea, 582 function short LHRH exposure, 552 effects of LHRH agonist, 456 LH receptors LHRH antagonist, 461 biosynthesis, 205 Leydig cell size function and turnover, 205 LHRH agonist, 486 induction, 255 Leydig cells spatial distribution, 203 binding LH-RH analogues, 441 LH release cyclic AMP levels, 480 acute stress, 514 LH receptors, 206 yamniobulyric acid, 12 pregnenolone and protein angiotensin 11, 16 phosphorylation, 431 bradykinin, 15 pregnenolone production, 427 calcitonin, 16 production of pregnenolone, cholinergic systems, 14 testosterone, 425 dopaminergic systems, 14 rat, 479 histamine, 12 regulation of steroidogenesis, aMSH, 17 423 noradrenergic systems, 14 testicular LHRH, 458 persistent activation, 132 LH pulsatile release, 13 hydroxycholesterol to testos• prostacyclin, 12 tosterone, 484 reduced caloric intake, 515 ovulatory surge and ovulation, serotonin, 12 605 vasotocin, 15 stimulates androgen, 290 LH-releasing activity stimulation of ovarian folli• Arg substitutions, 444 cles, 283 INDEX 617

LH responsiveness LH-RH (also LHRH) (continued) effect of OS, 256 release of LH, 4 LH secretion responsiveness, 4 LHRH-stimu1ated, 6 salmon brain, 446 LH secretory pattern sheep '8440 of hypothalamic amenorrhea, specificity for Arg , 478 581 spontaneous release, 95 LH surge steroidogenic enzymes, 468 effects of morphine, naloxone structure, 437 and combination, 514 structural heterogeneity, 442 LHS synthesized as precursor, 92 16-base oligomar, 402 synthesized ribosoma11y, 438 LH-FSH cells unique molecular form, 437 in gonadotropes, 194 vertebrate structures, 443 LH-RH (also LHRH) LH-RH agonist (also LHRH agonist) aromatase, 469 calcium, 483 aromatase activity, 468 chemical castration, 533 chicken hypothalamic, 442 cyclic AMP, 480 cholesterol side-chain cleav- cyclic AMP levels, 488 age, 470 decreased testosterone, 532 degradation, 103, 104, 108 direct stimulation of testos- degradation inhibitors, 121 terone, 460 degradation products, 118 endometriosis, 557 degradation by membrane bound hormone-dependent tumors, 558 enzymes, 118 increased testosterone from degraded by general proteo- 22 (R)-hydroxycho1estero1, 1yticenzymes, 105 485 degrading enzymes, 102 increases hydroxycho1estero1 diversity in structure, 438 to testosterone, 489 enzymes, 104 intratesticu1ar, 459 enzymes in regulation, 115 intratesticu1ar1y, 458 enzymatic hydrolysis, 102 rise in serum T and DHT, 534 fish, 444 stimulated 25-hydroxycho1estero1 frogs and toads, 443 to testosterone, 485 FSH release, 4 testicular androgen in man, 532 gonadal and placental, 441 testicular testosterone secre- in hypophysica1 portal blood, tion, 457 95 testosterone production, 482 LH-re1easing action, 5,608 testosterone secretion, 456 lizard and tortoise, 443 with antiandrogen, 533 localization, 3 LH-RH agonists mechanisms of action, 20 clinical use, 554 pituitary FSH, LH, 97 female contraception, 555 PRL and GH release, 358 gonadal and steroid secretion, PRL release, 356 554 prohormona1 species, 438 high dose, 554 by pulsatile infusion pumps, low dose, 554 552 male contraception, 556 618 INDEX

LH-RH agonists (continued) LHRH degradation pituitary refractoriness, 553 effects of, 122 precocious pubert reversible suppression of LHRH degrading enzymes pituitary and gonadal subcellular distribution, 110 function, 551 pituitary plasma membrane, 124 LHRH agonist and antiandrogen LH-RH fragments blood biochemistry, 539 isolation, 106 cortisol, dehydroepiandros• LHRH granules terone, 537 incubated with CuATP, 33 disappearance of bone lesions, incubated with CuHistidine, 35 538 isolation and incubation, 29 disappearance of pain, 538 LHRH-like peptide objective response, 539 Sertoli cells, 455 on serum PAP, 534 LH-RH-like pep tides PAP and testosterone, 536 in mammalian tissues, 438 perspiration and hot flashes, LHRH neurons 538 opioid peptides, 15 LHRH agonists and antioestrogens with cell axons, 3 hormone-dependent breast LHRH release cancer, 558 action of PGE 2, 11 LHRH agonist and LH copper-stimulated, 31 testosterone production, 483 CuATP-stimulated, 30 LH-RH analog epinephrine, 8 binding, 117 exocytosis, 27 modifications, 524 metal-ATP complexes, 30 substitutions, 525 norepinephrine, 8 LH-RH analogues role of MgATP, 28 degradation, 109 synaptic transmitters, 7 in bird, 446 LH-RH sequence LHRH and agonists within the prohormonal peptide, inhibit hormone-regulated 439 reproductive prosesses, LHRH-stimulated LH secretion 467 arachidonic acid, 6 LH-RH antagonist LH-RH super agonist hydrophilic-hydrophobic surface D-amino acids in position 6, model, 526 521 pro conformationally• LHRH synthesis restricting, 525 genomic control, 90 LHRH antagonists LH-RH variants block action of LHRH, 551 differences in positions seven receptor occupancy, 553 and eight, 447 LH-RH antagonist design LHRH-A amino acid replacements, 523 3S-hydroxysteroid dehydrogenase, LHRH control 472 noradrenergic and dopaminergic LHRH,a neurons, 10 cl~nical trials, 598 LH-RH decapeptide loci of action in rat, 593 antagonist studies, 521 pituitary in man, 595 INDEX 619

LHRHA (continued) Messenger molecules serum LH, 597 in plants, 83 sperm density, 598 Milk Proteins LHRH daily recombinant DNA clones, 386 LH, ~SH and testosterone, Milk protein gene expression 596 Hormonal regulation, 386 Lipozygenase Milk protein genes ovulation, 346 glucocorticoids and prolactin, Lower, Richard 385 Galen's hypothesis, 607 Milk protein mRNAs Luteal cell nucleic acid sequences, 385 aromatase, 292 Mitoses effects of Ca2+, 266 granulosa cells of follicle, effect of LH, 293 311 HDL receptors, 297 mLH-~ 5 8 ion-active drugs, 265 His ,Tyr and Arg hydrogen steroidogenesis, 303 bonding, 446 Luteal content Monerisin cho1estery1 ester and cho• release of prolactin, 173 lesterol, 300 Monkey Luteal function resistant to LHRH agonists, effect of LH or E, 291 532 Luteal membranes Morphine HDL binding, 298 blocks LH release, 513 Luteal phase Morphine and enkapha1in increased a-endorphin, 513 secretion of LH and FSH, 509 Luteal regression mRNAs sequence cellular mechanisms, 264 encoding a, LHa and FSHa, 403 Luteal tissue Muscarinic binding sit~~ progesterone and 20a-dihydro• acetylcholine and Ca ions, progesterone, 277 65 Luteinized theca cells Muscarinic receptors P to androgen, 295 adenohypophysis, 56 Luteo~~tic agents ~!ftagonists, 56 (Ca ) as intracellular Ca and estrogz!f' 68 mediator, 263 effects of Ca ,62 Luteotropic hormone effects of estrogen, 60 specific roles, 289 high to low affinity, 65 in peripheral and central nervous systems, 55 Mammary gland preoptic area, 62 model system, 385 steroid sex hormones, 58 Membrane compartments immunological specificity, 175 Nembutal Menstrual cycle and estrous prevention of preovulatory cycle surge, 340 key hormonal changes, 604 Neuro-G1 pep tides D-amino acid replacement, 527 620 INDEX

Neuropep tides Ovulation gonadotrophs and 1actotrophs, benzamidine, 345 356 effect of cysteine, 341 Neurotensin functional components, 337 LH and FSH levels, 45 Neurotransmitters influenced by opiates, 517 Paracrine factor Non-hormone messengers PRL release, 362 hormone-like, 73 PGF2a antagonizes action of LH, 264 inhibited cyclic AMP accumula• 01igodeoxynuc1eotide tion, 265 complimentary to mRNA, 401 Phosphatidy1inosito1 (P1) Oocyte ligand-receptor interaction, cumulus cell communication, 494 327 Phosphatidy1inosito1 (P1) cycle meiotic maturation, 325 sources of arachidonic acid uncoupled from cumulus cells, (AA), 495 333 Phosphatidy1inosito1 turnover Oocyte maturation in gonads, 500 blocked by dibutyryl cAMP, 326 in pituitary, 497 forskilin, 329 Phosphodiesterase LH, 331 cAMP accumulation, 414 Opiates forms in Serto1i granulosa dopamine inhibition, 368 cells, 415 Opioid FSH regulation, 412 LH release, 39 Phosphodiesterases release of LH, 41 granulosa cells, 416 Opioid pep tides hormone action, 420 in brain, 509 Phosphodiesterase stimulation Ouabain and monensin refractoriness, 417 inhibition of AMP and proges• Phospholipids terone, 266 from granulosa cells, 496 Ovarian cell regulation Phospholipid labeling role of purines, 265 in pituitary gonads, 496 Ovarian collagenase Pinocytotic activity activation, 340 in Amoeba proteus, 79 Ovarian follicles Pituitaries plasminogen activator, 343 incubation with LHRH, 116 Ovarian overstimu1ation plasma membranes, 115 mUltiple pregnancies, 590 Pitui tary cells Ovarian receptor specific receptors for hCG and DG-hCG binding, 226 s peptides, 370 Ovarian substance Pituitary GnRH receptors culture medium, 250 localization, 209 Pituitary gonadotrophs prostaglandin content, 347 receptors to GnRH, 208 Ovine corpus 1uteum Pituitary membranes no steroidogenic response, 274 photo labeled , 130 INDEX 621

Pituitary mRNAs Prostacyclin cell-free translation, 399 LH release, 12 Pituitary receptors Prostaglandin adenylate cyclase, 371 release LH and LHRH, 11 Plasminogen activator Prostablindins ovarlan follicles, 344 mediating effect of LH, 503 Poly A mRNA Prostate from , 90 androgens of adrenal origin, Pregnenelone 533 in stimulated cells, 253 Prostate cancer Pregnenolone production castration or estrogens, 531 isolated Leydig cells, 428 Prostatic cancer PRL late treatment, 542 subcellular localization, 173 Prostatic tissue PRL cells weak androgens into strong membrane antigens, 175 androgens, 540 models, 171 Prostatic tumors PRL release 99% androgen-sensitive, 540 superfused cell cultures, 358 Protein phosphorylation VIP, 359 effect of LH and LHRHa, 430 PRL releasing activity Protozoa pep tides , 363 ACTH, 77 20a-OH-P (progesterone) S-endorphin, 77 response to OS or FSH, 252 somatostatin, 77 Progesterone Pulsatile Gn-RH casein gene expression, 3k93 duration of follicular phase, synthesis, 471 587 Progesterone inhibition in hypothalamic amenorrhea, casein mRNA, 388 585 Progesterone production pregnancy rate, 589 OS enhancement, 254 Pulsatile secretion OS induced, 251 Gn-RH, 578 Progesterone synthesis Pycnosis catecholamines, 273 follicles, 311 Prolactin casein gene expression, 389 intracellular transit, 171 Receptor binding Prolactin cells deglycosylated hCG, 225 interaction, 368 receptors, 377 substances affecting, 367 Sauvagine Prolactin release ACTH output, 46 sauvagine, 47 similarities with eRF, 46 VIP and TRH, 369 suppress prolactin, 46 Prolactin secretion Secretory process sopamine receptor, 363 anterior pituitary cells, 169 short-loop feedback, 17 Serotonin somatostatin, 368 opiates on LH release, 517 VIP stimulation, 371 622 INDEX

Sertoli cells TRL adenylate cyclase, 418 PRL secretion by GH3 cells, S-adenergic agonists, 419 172 FSH, 412 phosphodiesterase, 418 Serum LH Unicellular organisms effects of MOR or NAL, 511 hormonal peptides, 78 gona4ectomy, 399 intercellular communication, 80 Serum LH and FSH messengers, 78 effects of morphine, met• up-ri.ulation enkaphalin and Ca -mediated, 161 Naloxone, 510 Serum progesterone in rabbits, 280 Vasopressin Sex steroid hormone prohormone, 438 antral fluid, 313 Vertebrate LH-RH Somatostatin gonadotropin-releasing activ• cyclic AMP, 375 ities, 444 GH secretion, 375 VIP in Tetrahymena pyriformis, 76 PRL release, 360 Somastatin binding VIP stimulation to prolactinoma membranes, adenylate cyclase, 372 378 VIP-stimulated adenylate cyclases Steroid production dopamine inhibition, 373 extracellular calcium, 433 Yeast Leydig cells, 432 diploids, 81 Steroidogenesis haplOids, 81 dependence upon estradiol, sex factors, 79 282 Yeast alpha factor Steroidogenic enzymes mimic WH, 79 interactions between FSH and LHRH, 473 Structure/ac~ivity relations LH-RH vertebrates, 446

Testicular LHRH biological effects, 463 Testicular steroidogenesis inhibition, 532 Testosterone female rats, 59 Testosterone production calsium concentrations, 482 regulated at three levels, 424 Thecal and granulosa cells interactions, 476