Binding studies of substance P anterior pituitary binding sites: changes in substance P binding sites during the rat estrous cycle.
Previous studies have shown that substance P (SP), an undecapeptide widely distributed in the gastrointestinal tract and in the peripheral and central nervous system, is a putative regulatory peptide involved in the control of reproductive function. Specifically, SP inhibited, at the anterior pituitary (AP) level, the stimulatory action of a physiological concentration (10(-8) M) of Gonadotropin Releasing Hormone (GnRH) on the release of the luteinizing hormone (LH). In the present work, we have demonstrated the presence of specific SP binding sites in the AP and related changes in the number of these sites to GnRH receptor number, hypothalamic SP and GnRH content and LH secretion during the rat estrous cycle. High affinity saturable SP binding sites (Kd, 1.5 approximately equal to 10 nM) were demonstrated in AP membranes using [3H]-SP or a novel analog, [125I]-(D-Tyr0, NorLeu11)SP. The binding affinity of SP fragments decreased with progressive removal of amino acid residues from N or C termini of the molecule. Other neuropeptides had low affinity for the SP binding sites. During the rat estrous cycle, SP and GnRH binding capacity of the anterior pituitary were inversely related. At the time of the proestrous LH surge, the AP binding capacity was low for GnRH but high for SP. The highest content of SP in the hypothalamus were recorded during the afternoon of proestrus when hypothalamic GnRH levels were lowest and the preovulatory surge occurred. These studies have established the presence of high affinity specific binding sites for SP in the AP which alter during the estrous cycle in a manner appropriate for mediating the direct inhibitory effects of SP on LH release in vitro.
Kerdelhué
B
B
Tartar
A
A
Lenoir
V
V
el Abed
A
A
Hublau
P
P
Millar
R P
RP
D000818:Animals; D004971:Estrus; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D010906:Pituitary Hormone-Releasing Hormones / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013373:Substance P / Q000031:analogs & derivatives / Q000378:metabolism; D013997:Time Factors
D010446:Peptide Fragments; D010455:Peptides; D010906:Pituitary Hormone-Releasing Hormones; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P; C042238:substance P, Tyr(1)-Nle(11)-; D007986:Luteinizing Hormone