Disease relevance of RT1-L

• Signaling via the G(i) subfamily of G proteins was excluded, as neither ERK activation nor c-Fos and LH beta induction was impaired by treatment with pertussis toxin or a cell-permeable peptide that sequesters G beta gamma-subunits [1].
• The nucleotide sequence of the gene encoding the beta-subunit of rat luteinizing hormone (LH beta) has been determined from a genomic DNA fragment cloned in lambda phage Charon 4A [2].
• LH released from a cell binds to adjacent RBCs bearing an LH Ab-protein A complex which results in a zone of complement-mediated hemolysis (a plaque) surrounding each gonadotrope [3].
• Pituitary cytoplasmic concentrations of GH and PRL mRNA were reduced in hypothyroidism and increased after administration of T3; LH beta mRNA was unaffected by hypothyroidism or T3 replacement [4].
• Exogenous hCG and LH can cause a modest hyperplasia in myometrial smooth muscle cells in culture [5].

High impact information on RT1-L

• Isolation and characterization of the rat LH beta gene further defines the evolution of glycoprotein hormone genes and will facilitate the study of cellular and molecular mechanisms which regulate LH beta gene expression [2].
• The pituitary gonadotropins FSH and LH are key hormones for regulating gametogenesis and steroidogenesis in the ovary and testis [6].
• In adult animals, LH receptor mRNA levels change dramatically during the estrous cycle, particularly after the preovulatory LH surge [6].
• We aimed to define the effects of testosterone (T) on alpha, LH beta, and FSH beta mRNA expression in the male rat after blockade of GnRH action on the gonadotrope [7].
• Our previous work demonstrated that in vivo estradiol (E2) administration to ovariectomized rats suppressed the transcription of the LH subunit genes within 4 h [8].

Biological context of RT1-L

• LH beta mRNA concentrations declined rapidly and had fallen to basal values by midnight on proestrus [9].
• These data suggest that small or medium-sized gonadotropes are activated during early diestrus to enlarge and produce LH beta [10].
• The percentage of cells bearing LH beta mRNA in the pituitary cell population increased from 6 +/- 0.4% in the evening of diestrous day 2 to 16 +/- 0.7% in the morning of estrus (average +/- SEM) [10].
• The down-regulation of LH receptors and blockage of the 17-hydroxylase/C17-20 lyase step in adult testis, and the absence of these responses in neonatal testis were confirmed [11].
• Thus, the up- and down-regulation of ovarian LH receptors during follicle growth, ovulation and luteinization is probably due, at least in part, to changes in receptor message modulation [12].

Anatomical context of RT1-L

• LHRH and sex steroids play a major and direct regulatory role in the secretion of LH by the anterior pituitary gland [13].
• An extensive morphometrical and microdensitometrical analysis of the various catecholamine (CA) cell groups of the medulla oblongata of the LL, LN and LH rats of the Lyon strain was performed [14].
• In the present study we have investigated the possible involvement of C/EBP proteins in regulating LH-dependent gene expression in Leydig cells [15].
• The induction of LH receptors in granulosa cells is prerequisite for ovarian follicles to ovulate and form corpora lutea [16].
• The differential effects of thyroid status on TSH, GH, PRL, and LH mRNA indicate specificity of regulation of these anterior pituitary hormone genes [4].

Associations of RT1-L with chemical compounds

• The aim of the present study was to investigate the interactions between sex steroids, more especially the potentiating effect of progesterone (P) in the presence or absence of a low dose of 17 beta-estradiol (E2) and/or dihydrotestosterone (D) on mRNA levels encoding the alpha- and beta-subunits of LH in both female and male rats [13].
• The influence of GnRH pulse frequency on LH subunit mRNA concentrations was examined in castrate, testosterone-replaced male rats [17].
• Furthermore, the present study illustrates the importance of the cumulative inhibitory effects of relatively low doses of E2 and D on mRNAs encoding both LH subunits [13].
• Thus, pulsatile GnRH in vivo is required to maintain transcription of the alpha-subunit and LH beta genes, with lesser effects on FSH beta [18].
• Between days 2 and 5 in culture in the absence of steroid treatment, steady state levels of LH beta and alpha-subunit mRNA declined (P less than 0.01) 52% and 61%, respectively, but FSH beta mRNA levels were unchanged [19].

Analytical, diagnostic and therapeutic context of RT1-L

• After castration in the male rat, there is a 2.5-fold increase in the percentage of gonadotropes and an increase in the proportion of gonadotropes storing both LH and FSH [20].
• Ovariectomy performed 14 days earlier, increased pituitary alpha and LH beta mRNA levels by 3.7- and 8.8-fold, respectively, while orchiectomy performed 14 days earlier increased alpha and LH beta mRNA levels by 6- and 6.5-fold, respectively [13].
• After incubation, total RNA was analyzed by Northern blot or dot blot hybridization with alpha- and LH beta 32P-labeled cRNA probes and mRNA levels were quantified by autoradiography [21].
• GnRH pulses (25 ng/pulse) or saline to controls, were given via a carotid cannula at intervals of 7.5-240 min for 48 h. alpha and LH beta mRNA concentrations were 109 +/- 23 and 30 +/- 5 pg cDNA bound/100 micrograms pituitary DNA, respectively, in saline controls [17].
• After treatment with the LHRH agonist (5 micrograms daily), the accumulation of mRNA encoding the alpha-subunit was stimulated by approximately 3-fold while the LH beta mRNA concentration remained unchanged [13].

References