Prolactin Suppression of Gonadotropin-Releasing Hormone Initiation of Mammary Gland Involution in Female Rats

It has been demonstrated that mammary gland involution after lactation is initiated by accumulation of milk in alveoli after weaning. Here, we report that involution is also dependent on mammary GnRH expression that is suppressed by PRL during lactation. Reduction of plasma prolactin (PRL) by the withdrawal of suckling stimuli increased GnRH and annexin A5 (ANXA5) expression in the mammary tissues after lactation with augmentation of epithelial apoptosis. Intramammary injection of a GnRH antagonist suppressed ANXA5 expression and apoptosis of epithelial cells after forcible weaning at midlactation, whereas local administration of GnRH agonist (GnRHa) caused apoptosis of epithelial cells with ANXA5 augmentation in lactating rats. The latter treatment also decreased mammary weight, milk production, and casein accumulation. Mammary mast cells were strongly immunopositive for GnRH and the number increased in the mammary tissues after weaning. GnRHa was shown to be a chemoattractant for mast cells by mammary local administration of GnRHa and Boyden chamber assay. PRL suppressed the mammary expression of both ANXA5 and GnRH mRNA. It also decreased mast cell numbers in the gland after lactation. These results are the first to demonstrate that GnRH, synthesized locally in the mammary tissues, is required for mammary involution after lactation. GnRH is also suggested to introduce mast cells into the regressing mammary gland and would be in favor of tissue remodeling. The suppression of these processes by PRL is a novel physiological function of PRL.

Effect of prolactin inhibition on thermoregulation, water and food intakes in heat-stressed fat-tailed male lambs

Two groups each of six lambs of the fat-tailed Naeimi breed, well adapted to a semi-arid climate, were housed under semi-controlled temperature (43·2 to 43·8°C) with low relative humidity (<0·8). After a 1-week adaptation period, the first group (control) was injected subcutaneously with 1 ml vehicle solution of 40% ethanol in saline, twice daily at 08.00 and 17.00 hfor the 11-day experimental period. In the other group, each lamb was injected daily for 6 days with 0·18 mg/kg per day of the prolactin inhibitor, 2 bromo-a-ergocryptine (CB154) dissolved in the vehicle solution. Treatment during the next 5 days was as for the control animals. Rectal temperature (RT), respiratory rate (RR), water and food intakes were recorded before injections. Daily average data were used in the statistical analysis, except those of the 1st day of bromocryptine injection. Lambs of the control group were able to maintain their RT (39·5 (s.e. 0·04) °C) during heat exposure, but those treated with the bromocryptine could not (40·3 (s.e. 0·07) °C). However, the latter group continued to respire more rapidly (P < 0·01) after cessation of the CB154 treatment, reducing their body temperature slightly (39·9 (s.e. 0·06) °C). This shows that, following prolactin suppression, heat-stressed lambs were unable to regulate their body temperature despite their RR. Water intake did not change during bromocryptine treatment, but the ratio of water to dry-matter intake did increase due to lower food consumption. These results suggest that prolactin might have an important role in thermoregulation of the fat-tailed male sheep during elevated ambient temperature.