S ite-specific decrease of progesterone receptor mRNA expression in the hypothalamus of middle-aged persistently estrus rats

MILLS, R.H., ROMEO, H.E., LU, J.K.H. AND MICEVYCH, P.E

BRAIN RESEARCH

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2002 vol. 995 p. 200 - 206

0006-8993

Middle-aged females gradually become acyclic and spontaneously develop a persistently estrus (PE) state. PE rats, acyclic for 30 days(early PE), are unresponsive to the positive feedback action of estrogen, but respond to a progesterone challenge with a luteinizinghormone (LH) surge and ovulation; unlike long-term PE rats, acyclic for 90 days, neither estrogen nor estrogen plus progesterone willelicit an LH surge [10th International Congress of Endocrinology, San Francisco, P3 (1996) 1061].We hypothesize that the PE state maydevelop due to a diminished level of estrogen-induced progesterone receptor (PR) expression in the hypothalamus that preventsprogesterone from stimulating LH regulating circuits. To test this hypothesis, PR mRNA levels were measured in hypothalamic regions ofyoung, proestrus (2?3 months of age), early PE (10?12 months) and long-term PE (13?15 months) rats. The anteroventral periventricularnucleus (AVPV), an important regulatory site of the LH surge, had decreased PR mRNA levels in early and long-term PE rats comparedwith proestrus rats. However, PR mRNA levels were reduced only in long-term PE rats in the ventromedial nucleus (VMH) and arcuatenucleus (ARH). In the medial preoptic nucleus (MPN), levels of PR mRNA did not change. A previous report showed that exogenousprogesterone stimulates an LH surge in young and early PE animals, indicating that the expression of PR mRNA demonstrated in thisstudy is sufficient to mediate progesterone facilitation of the LH surge in early PE rats. In acyclic, long-term PE rats, diminishedestrogen-induced expression of progesterone receptors is correlated with a previously shown inability to respond to exogenousprogesterone.