No abstract

This study examined alterations in episodic LH release in response to prolonged, slow infusions of dopamine (DA), norepinephrine (NE), or epinephrine (EPIN) into the third ventricle in adult, ovariectomized (OVX) rats, and the influence of priming with ovarian steroids on the LH response to the catecholamines. Unanesthetized rats with right atrial cannulae were bled continuously at slow rates for 1–1½ h prior to infusion, 1–1½ h during infusion, and up to 1 h afterwards. The amines were protected from oxidation by ascorbic acid, and infused in an artificial cerebrospinal fluid (CSF) vehicle (pH 7.29-7.33) into the third ventricle at a rate of 25–27 μl/h. Blood samples were analyzed for LH by radioimmunoassay. In unprimed, OVX rats, infusions of artificial CSF, as well as low doses of DA (2–4 μg/h) or NE (0.3–0.6 μg/h), had no effect on episodic LH release or mean blood LH levels. However, administration of 8.5 and l7μg DA/h, and 5.5 and 11 μg NE/h, resulted in a decrease in blood LH levels and, in most animals, prolonged intervals between peak blood LH levels during infusion or inhibitions which began rapidly and lasted for nearly the entire infusion period or longer. In contrast, infusion of 5.7 and 11.5 μg EPIN/h had no effect on blood LH levels in unprimed rats. In OVX rats primed 3 days prior to infusion with 50 μg estradiol benzoate and 25 mg progesterone (OEP), administration of CSF or the same doses of DA that previously inhibited episodic LH release had no effect on LH secretion. However, these steroids completely reversed the LH response to 11 μg NE/h, with increases in LH release occurring during infusion. EPIN, in doses ineffective in unprimed rats (5.7 and 11.5 μg/h), also caused elevations in blood LH levels in OEP rats. Finally, in rats primed with 5 μg estradiol benzoate/100 g b.w./day for the 2 days prior to infusion, none of the three neurotransmitters had any effect on LH release. These experiments indicate that in the absence of ovarian steroids intraventricular administration of DA can decrease mean blood LH levels and episodic LH release, and that this amine has no excitatory effect on LH release in steroid-primed rats. In contrast, NE and EPIN increased LH release in OEP rats, suggesting possible excitatory roles for both amines in the regulation of LH secretion. These data also indicate the critical importance of ovarian steroids in determining not only if a neurotransmitter (EPIN) can increase LH release, but also the direction in the LH response to a given neurotransmitter (NE). Finally, in addition to confirming the concept of an excitatory noradrenergic link in the regulation of LH release, studies in nonsteroid primed rats suggest the possible existence of noradrenergic receptors whose activation is subsequently inhibitory to episodic LH secretion.

This review considers some of the neuroendocrine factors influencing pulsatile LH secretion. Such release is apparently due to the pulsatile discharge of LHRH from brain peptidergic neurons. This is a physiologically important event since a periodic rather than continuous input signal to the pituitary gland prevents it from becoming refractory to LHRH stimulation. Pulsatile secretion of LH, in the rat at least, does not appear to be regulated solely by the medial basal hypothalamus. Central noradrenergic, cholinergic, dopaminergic, and serotoninergic systems are involved in influencing episodic LH release, presumably by affecting pulsatile LHRH secretion. Moreover, several hypothalamic as well as extrahypothalamic areas appear to play integral parts in controlling the rhythmic alterations in blood LH levels. These regions include the arcuate and suprachiasmatic nuclei, perisuprachiasmatic area, medial preoptic area, and midbrain dorsal raphe nucleus. Ovarian steroids also exert important influences on pulsatile LH release, and greatly modify the response of this secretory system to neurotransmitters and stimuli from certain brain regions.

The aim of this study was to determine whether the rapid increases in LH pulse amplitude and frequency that occur within 24 h after ovariectomy (ovx) on diestrus day 1 (D1) were due to the removal of progesterone (P) and/or estradiol (E). Initial studies demonstrated that plasma levels of E and P were 18.2 +/- 1.2 pg/ml and 34.1 +/- 3.2 ng/ml, respectively, between the evening of D1 and the morning of D2 in our colony of intact rats. Immediately after ovx and jugular venous cannulation on the morning of D1, rats were implanted either with empty Silastic capsules or capsules capable of restoring physiological levels of E and P to the control values reported above. These rats were continuously bled (75 microliter/6 min) for 3 h 1 day after ovx for analysis of pulsatile LH release, and then additional plasma samples were gathered for determination of E and P levels. Rats with empty capsules had decreased levels of E and P and increases in mean blood LH levels, LH pulse amplitude, and pulse frequency. Animals with E capsules had physiological levels of E and decreased levels of P, but no suppression of the acute post-ovx increase in pulsatile LH release. In contrast, animals with P capsules had physiological plasma levels of P, decreased levels of E, and a marked reduction in the acute LH response to ovx. This suppression was due entirely to a decrease in LH pulse amplitude, as pulse frequency was not altered. Rats with E and P capsules had physiological levels of these hormones, which resulted in an even greater reduction in the acute LH response to ovx. This suppression was due to decreases in both LH pulse amplitude and pulse frequency. The effect of P on LH pulse amplitude was centrally mediated, since the in vitro response to LHRH of anterior pituitary fragments from P-implanted rats was the same as that of anterior pituitary fragments taken from rats with empty capsules. These studies demonstrate that the acute increase in LH pulse amplitude that occurs within 24 h after ovx on D1 is due to the absence of a central inhibitory effect of ovarian P, while the rapid increase in LH pulse frequency is due to the loss of both ovarian E and P.(ABSTRACT TRUNCATED AT 400 WORDS)

This study was intended to examine the role of hypothalamic norepinephrine (HNE) and dopamine (HDA) in episodic luteinizing hormone (LH) release in adult ovariectomized rats. Unrestrained, unanesthetized rats with indwelling right atrial cannulae were bled continuously (30, 50, or 100 mul of whole blood/4-6 min for 3-4 hours), and the blood samples were analyzed for LH by radio-immunoassay. In other individual rats, changes in the hypothalamic levels of norepinephrine and dopamine after drug administration were determined by a radioisotopic-enzymatic catechol-O-methyl transferase assay. alpha-Methyl-p-tyrosine significantly decreased HNE and HDA concentrations but failed to alter episodic LH release. Two dopamine-beta-hydroxylase inhibitors (U-14,624 and FLA-63) caused marked reductions in HNE, small but not statistically significant increases in HDA, and an inhibition of episodic LH secretion. Apomorphine, a dopamine receptor stimulator, caused a transient (50-60 min) but marked inhibition of episodic LH release. Saline injection had no effect. Pimozide, a blocker of dopamine receptors, prevented the inhibitory effects seen following apomorphine. Although not studied in detail, pimozide alone did not appear to alter episodic LH secretion. These data suggest that in adult ovariectomized rats norepinephrine may be an excitatory neurotransmitter in the modulation of episodic LH release. The activation of dopamine receptors may be capable of inhibiting this release process. However, the apparent inability of pimozide alone to alter episodic LH discharge suggests that under physiological conditions dopamine may not play a role in the modulation of episodic LH secretion.