In most spontaneously ovulating mammals the corpora lutea formed at ovulation secrets progesterone for approximately 2 weeks. The corporalutea formed at ovulation in the rat secrete progesterone for only a few hours during the estrous cycle. However, a prolonged luteal phase or pseudopregnancy of approximately 2 weeks can be induced in the rat by mating or alternatively, by mechanical or electrical stimulation of the cervix on proestrus. Such stimulation leads to 10 days of daily nocturnal and diurnal surges of prolactin secretion from the pituitary gland. This hormone is responsible for maintenance of the corpus luteum. The cervical stimulus changes the activity of 2 areas of the hypothalamus to initiate these surges. Within the medial preoptic area, it turns off inhibitory neurons for nocturnal and diurnal surges and excites stimulatory neurons for diurnal surges of prolactin. Moreover, the stimulus excites stimulatory neurons for both surges within the dorsomedial-ventromedial areas of the hypothalamus. The prolactin-secretory response to cervical stimulation is further modified by ovarian and uterine input. The ovarian steroids either sensitize or inhibit prolactin secretion while the uterus secretes an unidentified activity which inhibits prolactin secretion directly at the pituitary level. Utilizing radioimmunologic estimates of hormone levels in blood, the chemical identity of the inhibitory and stimulatory input from the hypothalamus to the pituitary gland will be clarified. Moreover, the physiological role, the mechanism of action, and the chemistry of the uterine factor responsible for inhibiting prolactin secretion will be identified. The importance of these studies is that they will describe the nature of the hypothalamic response to a brief exteroceptive stimulus and furthermore will view the non-pregnant uterus as an endocrine organ whoe secretory product modifies pituitary prolactin secreted in response to that stimulus. Such studies also may suggest new methods of regulating fertility.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD011669-12
Application #
3311645
Study Section
Reproductive Biology Study Section (REB)
Project Start
1978-04-01
Project End
1993-05-31
Budget Start
1990-06-01
Budget End
1991-05-31
Support Year
12
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Florida State University
Department
Type
Schools of Arts and Sciences
DUNS #
020520466
City
Tallahassee
State
FL
Country
United States
Zip Code
32306
Kanyicska, B; Lerant, A; Freeman, M E (1998) Endothelin is an autocrine regulator of prolactin secretion. Endocrinology 139:5164-73
DeMaria, J E; Zelena, D; Vecsernyes, M et al. (1998) The effect of neurointermediate lobe denervation on hypothalamic neuroendocrine dopaminergic neurons. Brain Res 806:89-94
Rosso di San Secondo, V E; Fitch, C; Aniasi, A et al. (1998) Bromocriptine markedly inhibits progression of murine retrovirus-induced immunodeficiency. Transplant Proc 30:4128-9
Lerant, A; Freeman, M E (1997) Dopaminergic neurons in periventricular and arcuate nuclei of proestrous and ovariectomized rats: endogenous diurnal rhythm of Fos-related antigens expression. Neuroendocrinology 65:436-45
Lerant, A; Herman, M E; Freeman, M E (1996) Dopaminergic neurons of periventricular and arcuate nuclei of pseudopregnant rats: semicircadian rhythm in Fos-related antigens immunoreactivities and in dopamine concentration. Endocrinology 137:3621-8
Rosso di San Secondo, V E; Fitch, C; Aniasi, A et al. (1996) Bromocriptine prevents the immunosuppression induced in mice by anti-lymphocytic antiserum. Transplant Proc 28:3193-5
Kanyicska, B; Livingstone, J D; Freeman, M E (1995) Long term exposure to dopamine reverses the inhibitory effect of endothelin-1 on prolactin secretion. Endocrinology 136:990-4
Ergul, A; Glassberg, M K; Freeman, M E et al. (1994) A transformed murine Leydig cell line expresses the ETA receptor subtype. Mol Cell Biochem 136:91-6
Kanyicska, B; Freeman, M E (1993) Characterization of endothelin receptors in the anterior pituitary gland. Am J Physiol 265:E601-8
Arey, B J; Freeman, M E (1992) Activity of vasoactive intestinal peptide and serotonin in the paraventricular nucleus reflects the periodicity of the endogenous stimulatory rhythm regulating prolactin secretion. Endocrinology 131:736-42

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