Role of postnatal androgens in sexual differentiation of the lordosis-inhibiting effect of central injections of cholecystokinin.
The neuropeptide cholecystokinin (CCK) inhibits lordosis behavior when infused into the ventromedial nucleus of the hypothalamus (VMN) of female rats and has no effect when infused into the VMN of male rats. To test whether this sex difference develops under the control of perinatal steroids, male rats were castrated or given sham surgeries within 3 h of birth and female rats were injected with either 0 or 100 micrograms testosterone propionate on postnatal day 5. As adults, these rats were castrated as necessary, implanted with unilateral cannulae directed at the VMN, and tested for their ability to display female sexual behavior and to respond to CCK. Neonatal castration of males prevented defeminization of this response. When treated with 5 micrograms estradiol benzoate (EB), neonatally castrated males showed both lordosis behavior and a profound inhibition of that behavior after infusions of CCK. Neonatally castrated males did not display lordosis behavior when treated with 2 micrograms EB. Control males showed no lordosis behavior and, therefore, no response to CCK. Both doses of EB induced lordosis behavior in neonatally androgenized females. Significantly, these neonatally androgenized females were less responsive to CCK's inhibition of lordosis and were also anovulatory. These results imply that androgens alter the development of CCK responsive circuits as well as defeminize cyclic gonadotropin release. Levels of 125I-sCCK-8 binding in the VMN were correlated closely with an individual's ability to respond to sCCK-8. In summary, the inhibition of female sexual behavior caused by exogenously administered CCK in normal adult female rats appears to be controlled at least partially by levels of CCK receptors in the VMN and to differentiate under the control of perinatally present testosterone.
Department of Anatomy and Cell Biology, UCLA School of Medicine, 90024-1763.
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Ulibarri
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Popper
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Micevych
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000502:physiology*; D002766:Cholecystokinin / Q000494:pharmacology*; D004958:Estradiol; D005260:Female; D007267:Injections; D008297:Male; D011187:Posture; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D012726:Sexual Behavior, Animal
D000728:Androgens; D004958:Estradiol; D002766:Cholecystokinin