Date of Award

1-1-1979

Embargo Period

4-18-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Physiology

College

College of Graduate Studies

First Advisor

J.G. Ondo

Second Advisor

H. Jonsson Jr.

Third Advisor

D.D. Wheeler

Fourth Advisor

W.C. Wise

Fifth Advisor

Donald L. Wilbur

Abstract

Prolactin secretion following the injection of thyrotropin releasing hormone (TRH) was characterized in unanesthetized freely moving female rats at various times during the estrus cycle. Pituitary responses to TRH were also studied using prepubertal and ovariectomized animal models. Subsequent experiments examined the involvement of ovarian steroids and dopamine in the pituitary response to TRH. Initial studies determined the range of TRH doses that elicited minimal through maximal elevations in prolactin secretion in prepubertal, ovariectomized, and mature intact animals in estrus and diestrus. Dose response studies demonstrated that increases in prolactin secretion occurred with increasing amounts of TRH in all animals. For a given dose of TRH, maximal pituitary responses were greater in mature normal animals than either prepubertal or ovariectomized animals. Significant alteration in prolactin secretion in response to TRH occurred in animals during the estrus cycle. Greatest pituitary responses developed on the afternoon of proestrus, while the lowest responses were measured in animals in diestrus. The role of ovarian steroids in the modulation of pituitary responses to TRH was evaluated using normal mature, ovariectomized, and prepubertal animals. An acute one hour infusion of estradiol or progesterone failed to alter responses of the pituitary to TRH in proestrus A.M. animals. Administration estradiol for two days (10 ug/day) in ovariectomized and prepubertal animals had no significant effect on prolactin secretion following injection of TRH. However, progressive reductions in pituitary responses to TRH were observed in animals with increasing time following ovariectomy. Further studies examined whether changes in pituitary content of prolactin or number of receptors to TRH might be involved in the differences observed in pituitary responses to TRH. Both prolactin content and receptor level for TRH in ovariectomized and prepubertal animals were reduced below those measured in normal mature animals. Total pituitary of prolactin and TRH receptor levels closely paralleled the changes in pituitary response to TRH that occurred during the estrus cycle. Although estradiol increased receptor levels and pituitary prolactin content, pituitary responses to TRH remained low in estrogen treated ovariectomized animals. Multiple injections or prolonged infusions of TRH were used to characterize the pituitary responses to varied input modes of TRH. Maximal prolactin responses to repeat injections of TRH spaced 10 minutes apart were dose dependent. Incremental prolactin responses to first and second injections of 100 ng of TRH were equal. With higher doses of TRH (500-5,000 ng), pituitary responses to the second injections were reduced. Constant infusion of TRH (10 ng/min x 60 min) failed to maintain elevated prolactin levels in estrus animals. Diestrus animals failed to respond at all. Pituitary responses to subsequent injection of TRH or haloperidol indicated that adequate prolactin remained in the pituitary following the TRH infusion. The interactions of TRH with haloperidol and dopamine were examined. Infusions of dopamine (1000, 10, and 0.001 ng/min) do not influence pituitary prolactin responses to TRH, although endogenous prolactin secretion is significantly reduced. Pituitary prolactin responses to haloperidol 10 ug, i.v.) were greater in estrus than diestrus animals. Haloperidol stimulated of prolactin secretion was significantly greater than that by TRH. When TRH and haloperidol were administered consecutively, prolactin responses to each secretagogue were found to be independent and additive. Maximum prolactin responses to both TRH and haloperidol were significantly greater in normal female animals than ovariectomized animals. The combined results of these experiments suggest that changes in response of the pituitary to hypothalamic regulation occur during the estrus cycle. Additional increases in pituitary response to TRH during the estrus cycle may be modulated by estrogens, through their effects on pituitary hormone content and hypothalamic neurohormone receptors. However, the inhibitory effects on prolactin secretion by dopamine do not modulate prolation response to TRH. It can therefore be theorized that prolactin may exist within the pituitary as two functionally separate pools. A small pool may be released through direct stimulation by TRH or other hypothalamic prolactin releasing factors. The second larder pool may be regulated through the inhibitory action of dopamin or prolactin inhibiting factors, and is the main source of prolactin during the midcycle hormone surge.

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