title: Impact of growth hormone resistance on female reproductive function: new insights from growth hormone receptor knockout mice.
abstract: We examined multiple aspects of reproductive function in growth hormone receptor gene knockout (GHR-KO) and normal mice to clarify the role of growth hormone in female reproduction. In adult animals, estrous cycle duration was comparable in all mice housed individually but was significantly longer in group-housed GHR-KO females. Histological evaluation of ovaries of adult females at estrus showed that the numbers of preovulatory follicles and corpora lutea were significantly reduced in GHR-KO mice, as was the plasma estradiol level. The number of atretic preovulatory follicles was reduced in GHR gene-ablated animals. Although reverse transcription polymerase chain reaction analysis revealed reduced ovarian insulin-like growth factor I (IGF-I) mRNA expression in GHR-KO females, the expression of several steroidogenic enzyme mRNAs did not differ between groups. The numbers of active corpora lutea and uterine implantation sites were reduced in GHR-KO females at Day 7 of gestation. When young females were mated to normal males, latency to first mating and age of the female at first mating were significantly delayed in GHR-KO females, but maternal age at first conception was similar between groups. Significantly fewer virgin GHR-KO females exhibited pseudopregnancies when initially placed with vasectomized normal males than did normal female counterparts. Growth hormone resistance and IGF-I insufficiency negatively impacted 1) follicular development/ovulation rate, 2) sexual maturation, 3) production of and responsiveness to pheromonal signals, and 4) the ability of virgin females to respond to coitus by activation of luteal function. Although GHR-KO female mice are fertile, they exhibit quantitative deficits in various parameters of reproductive function.
authors.affiliation: Department of Physiology, School of Medicine, Southern Illinois University, Carbondale 62901-6512, USA. dzaczek@siumed.edu
authors.forename: Denise
authors.initials: D
authors.lastname: Zaczek
authors.forename: James
authors.initials: J
authors.lastname: Hammond
authors.forename: Lii
authors.initials: L
authors.lastname: Suen
authors.forename: Serge
authors.initials: S
authors.lastname: Wandji
authors.forename: Darlene
authors.initials: D
authors.lastname: Service
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bartke
authors.forename: Varadaraj
authors.initials: V
authors.lastname: Chandrashekar
authors.forename: Karen
authors.initials: K
authors.lastname: Coschigano
authors.forename: John
authors.initials: J
authors.lastname: Kopchick
mesh_terms: D000375:Aging; D000818:Animals; D003338:Corpus Luteum / Q000502:physiology; D004351:Drug Resistance; D010064:Embryo Implantation; D030762:Estrous Cycle; D004973:Estrus Synchronization; D005260:Female; D005838:Genotype; D013006:Growth Hormone / Q000494:pharmacology / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D006080:Ovarian Follicle / Q000033:anatomy & histology / Q000502:physiology; D010053:Ovary / Q000033:anatomy & histology / Q000502:physiology; D010060:Ovulation; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D011986:Receptors, Somatotropin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D012098:Reproduction / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012741:Sexual Maturation; D014599:Uterus / Q000033:anatomy & histology / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone