TY - JOUR
T1 - Facilitation or inhibition of the estradiol-induced gonadotropin surge in the immature rat by progesterone
T2 - Regulation of GnRH and LH messenger RNAs and activation of GnRH neurons
AU - Attardi, Barbara
AU - Klatt, Brian
AU - Hoffman, Gloria E.
AU - Smith, M. Susan
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1997/8
Y1 - 1997/8
N2 - We have developed and extensively characterized immature female rat models to demonstrate inhibition or facilitation of the estradiol (E2)-induced gonadotropin surge by progesterone (P). We show here that the surge of free α-subunit is regulated similarly by P in these models. To investigate the possibility that P alters the biosynthesis of GnRH and/or LH, we measured levels of LH subunit mRNAs by Northern blot hybridization and GnRH mRNA by a solution hybridization-RNase protection assay. In the P inhibition model, α-subunit mRNA was significantly decreased when P was administered together with E2 for 32 or 48 h, and LHβ, at 29 h. In the facilitation model, neither α-subunit nor LHβ mRNA increased with premature and enhanced release of LH and free α-subunit. Levels of GnRH mRNA in E2-treated rats were significantly higher on the afternoon of the LH surge than on that or the following morning. There was no effect of P on GnRH mRNA levels, however, before, during, or after the LH surge in either paradigm. The time course of activation of GnRH neurons in P-facilitated rats was determined by double-label immunocytochemistry for GnRH and cFos. When serum LH concentrations were basal there was no expression of cFos in GnRH neurons. LH secretion in P-facilitated rats was initiated at ≃ 14.00 h and remained elevated until at least 19.00 h. During this time 63-78% of GnRH neurons were cFos positive. Both serum LH concentrations and the percentage of cFos-activated GnRH neurons were significantly lower in control rats treated with E2 alone than in those treated also with P. In conclusion: 1) suppression of LH acid free α-subunit secretion by P can be accounted for at least partly by suppression of α-subunit mRNA levels; 2) P facilitation is not associated with changes in LH subunit or GnRH mRNA levels; 3) the large proportion of cFos-positive GnRH neurons in P-facilitated rats closely parallels increases in serum LH concentrations but is not accompanied by changes in GnRH mRNA levels. It is likely, therefore, that P acts in the facilitation model to trigger release of pre-existing GnRH stores by altering synthesis or activity of neuro-transmitters/neuropeptides involved in GnRH regulation and/or release of LH stores by altering, for example, pituitary responsiveness to GnRH (including self-priming) and components of the LH secretory apparatus. Similar possibilities may also obtain for the blockade of the gonadotropin surge in the inhibition model.
AB - We have developed and extensively characterized immature female rat models to demonstrate inhibition or facilitation of the estradiol (E2)-induced gonadotropin surge by progesterone (P). We show here that the surge of free α-subunit is regulated similarly by P in these models. To investigate the possibility that P alters the biosynthesis of GnRH and/or LH, we measured levels of LH subunit mRNAs by Northern blot hybridization and GnRH mRNA by a solution hybridization-RNase protection assay. In the P inhibition model, α-subunit mRNA was significantly decreased when P was administered together with E2 for 32 or 48 h, and LHβ, at 29 h. In the facilitation model, neither α-subunit nor LHβ mRNA increased with premature and enhanced release of LH and free α-subunit. Levels of GnRH mRNA in E2-treated rats were significantly higher on the afternoon of the LH surge than on that or the following morning. There was no effect of P on GnRH mRNA levels, however, before, during, or after the LH surge in either paradigm. The time course of activation of GnRH neurons in P-facilitated rats was determined by double-label immunocytochemistry for GnRH and cFos. When serum LH concentrations were basal there was no expression of cFos in GnRH neurons. LH secretion in P-facilitated rats was initiated at ≃ 14.00 h and remained elevated until at least 19.00 h. During this time 63-78% of GnRH neurons were cFos positive. Both serum LH concentrations and the percentage of cFos-activated GnRH neurons were significantly lower in control rats treated with E2 alone than in those treated also with P. In conclusion: 1) suppression of LH acid free α-subunit secretion by P can be accounted for at least partly by suppression of α-subunit mRNA levels; 2) P facilitation is not associated with changes in LH subunit or GnRH mRNA levels; 3) the large proportion of cFos-positive GnRH neurons in P-facilitated rats closely parallels increases in serum LH concentrations but is not accompanied by changes in GnRH mRNA levels. It is likely, therefore, that P acts in the facilitation model to trigger release of pre-existing GnRH stores by altering synthesis or activity of neuro-transmitters/neuropeptides involved in GnRH regulation and/or release of LH stores by altering, for example, pituitary responsiveness to GnRH (including self-priming) and components of the LH secretory apparatus. Similar possibilities may also obtain for the blockade of the gonadotropin surge in the inhibition model.
KW - GnRH
KW - LH surge
KW - Progesterone
KW - cFos
KW - α-subunit
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U2 - 10.1046/j.1365-2826.1997.00610.x
DO - 10.1046/j.1365-2826.1997.00610.x
M3 - Article
C2 - 9283047
AN - SCOPUS:0030751369
SN - 0953-8194
VL - 9
SP - 589
EP - 599
JO - Journal of Neuroendocrinology
JF - Journal of Neuroendocrinology
IS - 8
ER -