Divergent Effects of Estradiol on Gonadotropin Gene Transcription in Pituitary Fragments

Abstract

Our previous work demonstrated that in vivo estradiol (E2) administration to ovariectomized rats suppressed the transcription of the LH subunit genes within 4 h. To determine whether these effects were mediated directly at the level of the gonadotrope, the transcription rates of the LH beta, FSH beta, and alpha-subunits were measured in short term cultures of pituitary fragments from female rats in various physiological states. In each in vitro experiment, fragments from matched sets of hemipituitaries were used for control and treatment (10(-8)ME2) groups. In pituitaries from ovariectomized animals, treated in vitro with or without E2, there was no significant effect of 2 h or 6 h of E2 on FSH beta or alpha-subunit gene transcription, but a consistent 2- to 3-fold stimulation of LH beta mRNA synthesis. In pituitaries from intact randomly cycling rats, E2 in culture had no effect on the transcription rate of alpha-subunit, FSH beta, or TSH beta genes, but stimulated LH beta and PRL transcription 2-fold. Thyroid hormone treatment specifically suppressed alpha-subunit (38% of control) and TSH beta (17% of control) mRNA synthesis, indicating that the culture system is responding in an appropriate physiological manner and that decreases in transcription can be easily and accurately measured with this system. Basal and E2-treated transcription rates for each gonadotropin subunit gene were measured as a function of stage of the estrous cycle. Basal transcription of the alpha-subunit gene did not vary significantly throughout the cycle and did not respond to E2 treatment in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)