Further characterization of tolerance to the corticosterone-elevating effect of pergolide in rats.

Four daily injections of pergolide, an ergoline dopamine agonist, made male rats tolerant to the corticosterone-elevating effects of an acute injection of pergolide on the fifth day. This tolerance occurred not only to acute treatment with pergolide, but also to other dopamine agonists differing in structure, potency and receptor subtype selectivity. Plasma corticosterone was elevated following administration of opioid or serotonin agonists in both vehicle- and pergolide-pretreated rats. The current findings strengthen the conclusion that tolerance to the acute elevation of corticosterone by pergolide is not due to impairment of pituitary-adrenocortical function but instead to changes in dopamine receptors that initiate the response.

Concentrations of luteinizing hormone, follicle stimulating hormone and prolactin following transection of the pituitary stalk in ovariectomized ewes.

Two experiments (Spring and Fall) were conducted in ovariectomized ewes to determine changes in pituitary hormone secretion immediately after pituitary stalk-transection. Ewes underwent either pituitary stalk-transection (SS), sham-transection (SH) or administration of anesthesia only (AO). Stalk-transected, but not sham-operated or anesthetized ewes had polyuria and polydipsia for 7 to 14 days after surgery. Concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin were measured in peripheral blood samples collected every 10 minutes for a six-hour period. Results were comparable for each season. During the six hours following surgery or removal from anesthesia, concentrations of LH declined in all ewes, but more slowly in SS ewes. No differences in patterns or mean concentrations of FSH were observed. Immediately after surgery, concentrations of prolactin were elevated, then declined in SH and SS ewes. The decrease was greater in SH than SS ewes. Data are consonant with the view that hypothalamic inhibition as well as LHRH stimulation regulate gonadotropin release by the pituitary.

Relationships between LH and estradiol-17 beta after removal of luteal progesterone in the ewe.

Three experiments were conducted to examine the relationship between systemic concentrations of luteinizing hormone (LH) and estradiol-17 beta (E2) after withdrawal of progesterone in cycling ewes. In Exp. 1, ewes were assigned randomly to one of three treatments: laparotomy (C), removal of the luteal ovary (ULO), or ULO plus anesthesia with sodium pentobarbital for 6 h beginning 4 h after surgery. Anesthesia was used in an attempt to block the expected increase in tonic secretion of LH. Patterns of LH and E2 in these three groups did not differ during the 24-h experimental period. In Exp. 2, a longer period of anesthesia was utilized. Forty-eight ewes were assigned at random to one of four treatments: C, ULO, lutectomy or an intrafollicular injection of prostaglandin F2 alpha (PGF2 alpha). One-half of the ewes in each group were anesthetized with sodium pentobarbital from initiation of treatment (0 h) until 10 h after surgery. Sodium pentobarbital did not suppress the increases in LH and E2 after progesterone withdrawal. The regression of concentrations of E2 on concentration of LH was not significant. In Exp. 3, ewes were infused with either saline or dopamine after receiving an im injection of PGF2 alpha. Tonic secretion of LH increased after 4 h in ewes infused with saline, but not in ewes infused with dopamine. Despite the suppression of LH, concentrations of E2 increased in dopamine-treated ewes as in control ewes. Therefore, the initial increase in E2 after a decline of progesterone in cycling ewes is independent of increases in LH.

Endocrine and neurochemical effects of (+)-PHNO, a dopamine D2 agonist.

The naphthoxazine compound, (+)-PHNO, is a dopamine D2 receptor agonist which acts within the central nervous system. The effects of this drug on serum concentrations of corticosterone and prolactin and on brain concentrations of catecholamines and some of their metabolites were determined in male rats. Administration of (+)-PHNO in doses ranging from 3-300 micrograms/kg i.p. resulted in increased serum corticosterone, decreased serum prolactin and decreased concentrations of the dopamine metabolites, DOPAC and HVA, in the brain. At the higher doses of (+)-PHNO, concentrations of MHPG sulfate in the brain stem were increased and hypothalamic epinephrine concentrations were decreased. Pretreatment with centrally acting dopamine antagonists (spiperone or haloperidol) prevented the (+)-PHNO-induced changes in serum corticosterone, prolactin and brain catecholamines. In contrast, pretreatment with halopemide, a dopamine antagonist which penetrates poorly into the brain, was unable to block the effects of (+)-PHNO on serum corticosterone and brain catecholamines. These data show that (+)-PHNO, a dopamine agonist structurally unrelated to other dopamine agonists, acts centrally to affect serum corticosterone and brain catecholamines.