The effect of oestradiol and progesterone on hypoglycaemic stress-induced suppression of pulsatile luteinizing hormone release and on corticotropin-releasing hormone mRNA expression in the rat.
Corticotropin-releasing hormone (CRH) is implicated in the suppression of pulsatile luteinizing hormone (LH) secretion by a variety of stressful stimuli; 17beta-oestradiol (E2) has been shown to modulate this inhibitory response. The present study in ovariectomized (OVX) rats was designed to investigate the effect of E2 and progesterone (P4) on hypoglycaemic stress-induced changes in pulsatile LH secretion and on the associated changes in both central and peripheral components of the hypothalamic-pituitary-adrenal axis. E2 enhanced the hypoglycaemic stress-induced suppression of LH pulses; P4 in addition to E2 further potentiated the inhibitory response. The rise in plasma corticosterone following insulin-induced hypoglycaemia (IIH) was highest in the E2 + P4 group. Nevertheless, when such levels were achieved by administration of corticosterone, the occurrence of LH pulses was completely unaffected, irrespective of ovarian steroid milieu. E2 and E2 + P4 up-regulated basal CRH mRNA expression in the paraventricular nucleus (PVN) as measured by in situ hybridization; this signal was also increased in the medial preoptic nucleus (MPN) following E2. IIH resulted in a rise in CRH mRNA in the PVN, but not in the MPN; this rise may reflect a more significant role for the PVN in the present context. Changes in neuropeptide mRNA expression may signal changes in neuronal activity; nevertheless, the profound differences in LH pulse suppression in OVX, E2 and E2 + P4 rats following IIH were not reflected in the concurrent changes in CRH mRNA in the PVN. The results suggest that while corticosterone has no acute effect on LH pulses in the rat, the up-regulation by ovarian steroids of basal CRH mRNA in the PVN and/or MPN may contribute to the central regulation of these pulses in response to stress.
Li
X F
XF
Centre for Reproduction, Endocrinology and Diabetes, GKT School of Biomedical Sciences, King's College London, London, UK.
Mitchell
J C
JC
Wood
S
S
Coen
C W
CW
Lightman
S L
SL
O'Byrne
K T
KT
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007003:Hypoglycemia / Q000503:physiopathology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D010052:Ovariectomy; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry; D010507:Periodicity; D011301:Preoptic Area / Q000737:chemistry; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000503:physiopathology*
D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone