Studies were undertaken to (1) examine the effects of hyperprolactinemia on the frequency and amplitude of pulses of LH, and (2) determine if changes in pituitary sensitivity to LHRH were involved in the prolactin-induced suppression of LH secretion. Rats were bilaterally ovariectomized (day 0). Ovine prolactin (4 mg/kg body weight, subcutaneously) or vehicle was administered every 8 h beginning at 09.00 h on day 4 after ovariectomy and continuing until 09.00 h on day 6. On day 6, between 07.00 and 09.00 h all animals received a right atrial cannula, using ether anesthesia. In experiment I blood samples were taken at 10-min intervals beginning at 12.00 h on day 6, for a total of 180 min. To test the effect of hyperprolactinemia on pituitary responsiveness (experiment II) animals received an intravenous injection of LHRH (25 ng/100 g body weight) after the 180-min and again after the 240-min sample. Blood was drawn every 10 min for a total of 300 min. Serum was assayed for LH. Hyperprolactinemia altered the pattern of pulsatile secretion of LH. Treatment with ovine prolactin produced a decrease in both the frequency and amplitude of the LH pulses compared to values found in control animals. However, no differences in pituitary responsiveness between hyperprolactinemic and control animals were found at the dose of LHRH given. Thus, the prolactin-induced suppression of pulsatile secretion of LH was not apparently a result of alterations in the sensitivity of the pituitary to LHRH. From these studies we suggest that hyperprolactinemia directly affects a hypothalamic site which ultimately alters the LHRH pulse generator, thereby changing the secretion of LHRH.

Because of some indication that FSH secretion is less dependent than LH secretion on GnRH in vivo, we performed experiments to examine the effects of a GnRH antagonist (antag) on LH and FSH secretion. We first showed that pituitary cells superfused with GnRH showed a similar pattern of suppressed secretion of both LH and FSH in response to addition of antag. In contrast, antag administration to ovariectomized rats had differing effects on LH and FSH secretion. Serum LH was suppressed in a dose-dependent fashion by 2 h (20–50% of control values). Recovery from the lower doses of antag was seen by 12 h, but the two highest doses maintained serum LH levels at 10% of control values for 72 h. In contrast, the effect on serum FSH was not manifested until 12 h. FSH was maximally decreased only to 40–60% of control values. The two highest doses maintained this effect for 72 h. These results reinforce previous suggestions that FSH secretion in vivo may occur independently of acute changes in GnRH secretion, and may have an GnRH-independ-ent component.

No abstract

The inhibitory effects of acute hyperprolactinemia on the cyclic release of LH and PRL were examined in the ovariectomized estradiol-treated rat. In Exp 1, animals were ovariectomized (day 0) and received sc injections of ovine (o) PRL (4 mg/kg BW) or vehicle beginning at 0900 h on day 4, 6, or 7 postovariectomy and continuing every 8 h until 0900 h on day 9. All animals were given Silastic capsules containing estradiol (E2) on day 7, were cannulated via the external jugular vein on day 8, and were bled at 0900 and 1030 h and at hourly intervals between 1200-1800 h on day 9. No effect of oPRL treatment on the cyclic release of LH was seen in 1-week ovariectomized rats regardless of the duration of PRL treatment. The endogenous rat PRL surge was attenuated by treatment with oPRL. In Exp 2, animals were ovariectomized (day 0) and, beginning on day 11 or 14 postovariectomy, received sc injections of oPRL or vehicle every 8 h until 0900 h on day 16. On day 14, animals received Silastic E2 capsules. The following day (day 15), the external jugular vein was cannulated, and at 1800 h, E2 capsules were removed from half of the rats. On day 16, rats were bled at the times outlined in Exp 1. When E2 levels were maintained by the continuous presence of an E2 capsule, hyperprolactinemia did not suppress the cyclic release of LH and only attenuated or shifted the timing of the rat PRL surge. In marked contrast, when E2 stimulation was discontinuous, oPRL abolished the steroid-induced LH surge in all animals treated with oPRL beginning on day 11 and in 57% of the animals treated beginning on day 14. Treatment with oPRL abolished the endogenous PRL surge in all animals regardless of the duration of PRL exposure. In conclusion, oPRL-induced hyperprolactinemia can inhibit E2-induced LH and PRL surges in long term ovariectomized rats under conditions of discontinuous E2 exposure. In contrast, when estrogen levels are maintained, hyperprolactinemia had no effect on the LH surge and only attenuated or shifted the timing of the endogenous PRL surge. Thus, the long term ovariectomized rat receiving discontinuous E2 provides a model that is particularly suited for the study of the possible neural mechanisms by which PRL inhibits cyclic release of LH.

Dopamine (DA), norepinephrine (NE), epinephrine (E), 3,4-dihydroxyphenylglycol (DOPEG) and dihydroxyphenylacetic acid (DOPAC) were determined simultaneously by a radioenzymatic, thin-layer chromatographic assay able to detect 1-10 pg of the parent compounds and 80-120 pg of their metabolites. A localization study of these compounds in 20 micro-dissected hypothalamic and limbic structures and the anterior and posterior pituitary glands of male rats was completed. DOPAC was detectable in 14 of 22 structures with the lowest DOPAC/DA ratio being found in the caudate nucleus (7.1%) and the highest in the medial aspect of the ventromedial nucleus of the hypothalamus (422.0%). There was a higher DOPAC/DA ratio in the lateral (21.5%) than in the medial (11.3%) portion of the median eminence suggesting that a greater portion of released DA in the medial median eminence enters the portal circulation. DOPEG was detectable in 6 of 22 structures with DOPEG/NE ratios ranging from 8% (interstitial nucleus of the stria terminalis, ventral aspect) to 32% (medial median eminence). A poor correlation exists between DOPAC and DA concentrations in the various brain regions while there was a stronger relationship between DOPEG and NE concentrations. Male rats were rendered hyper-prolactinemic for 48 hours with injections of ovine prolactin (oPRL) every 8 hours (4 mg/kg body weight sc). In such rats there was a suppression of endogenous rat PRL (rPRL) secretion, the DOPAC/DA ratio increased 2.2-fold in the medial (MEm) and 1.9-fold in the lateral median eminence (MEl), and the DA concentration in the anterior pituitary also increased 2.6-fold. In 10 day postpartum lactating rats, suckling produced marked increases in serum rPRL but no change in DOPAC/DA ratios in the ME or in the DA concentration in the anterior pituitary. The data reveal a wide range of DOPAC/DA ratios (7-422%) in brain regions containing cell bodies, axons and terminals of the different dopaminergic neuronal tracts in brain and pituitary. Considering the DOPAC/DA ratios in the MEm and MEl, it is suggested that a large perturbation of dopaminergic transmission produces a significant ratio change while a smaller perturbation is not detected by this index of neuronal metabolism.