The regulation of oxytocin receptor binding in the ventromedial hypothalamic nucleus by gonadal steroids.
In the previous sections, data were presented on the regulation of OT receptor binding by gonadal hormones. However, it is important to emphasize that gonadal steroids and E2 in particular also regulate other facets of OT transmission. For example, OT peptide levels as indicated by mRNA levels and OT immunoreactivity are enhanced by gonadal steroids. Similarly, OT release is also influenced by circulating steroids. By focusing on data collected in female rats and combining these different factors, the following relationships emerge. Within the ventromedial hypothalamus, OT peptide levels are virtually undetectable and OT receptor binding is negligible in the absence of E2. As circulating levels of E2 rise, increases in OT immunoreactivity and OT-receptor binding in the ventromedial hypothalamus and in the VMN itself can be detected. Under these conditions, OT receptor binding in and around the vl-VMN is markedly increased, rendering cells in the vl-VMN responsive to OT stimulation. Significantly, this increased responsivity is most evident at low concentrations of OT. With further increases in E2, P4 is released from the ovary, resulting in a number of biochemical changes in the central nervous system, including a potentiation of the effects of E2 on hypothalamic OT-receptor binding. Within a few hours after the initiation of P4 release, sexual receptivity can be elicited. At this time, sexual contact by the male enhances OT-peptide levels in the ventromedial hypothalamus of steroid-primed female rats, which in turn potentiates the display of sexual receptivity. The model outlined above not only summarizes a large portion of the data on steroid regulation of hypothalamic OT receptors, but more importantly, serves to highlight areas that require additional study. One important question that remains to be resolved is the source of OT receptors in the ventromedial hypothalamus. While the lesion studies discussed above indicate that the majority of fibers in the ventrolateral hypothalamus originate in the VMN, definitive results can only be obtained with more direct methods. For example, following the eventual cloning and sequencing of the OT receptor, studies on the distribution and regulation of OT receptor mRNA could be conducted to determine the hypothalamic cells that synthesize OT receptors. Complementary experiments that employ an immunohistological approach in combination with electron microscopy could be used to visualize the region(s) of the cell that react to OT receptor antibodies. Additional studies are also required to determine the role of steroid-modulated OT receptor binding in the hypothalamus of male rats.(ABSTRACT TRUNCATED AT 400 WORDS)
Johnson
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AE
Karolinska Institute, Huddinge Hospital, Sweden.
D000818:Animals; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology* / Q000502:physiology; D004971:Estrus / Q000378:metabolism; D005260:Female; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism*; D018045:Receptors, Oxytocin; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism*
C055830:KB 5-21; D011945:Receptors, Angiotensin; D018045:Receptors, Oxytocin; D013196:Dihydrotestosterone; D011374:Progesterone; D004958:Estradiol; D010121:Oxytocin