Involvement of Endogenous Opioidergic Neurons in Modulation of Prolactin Secretion in Response to Mating in the Female Rat

Abstract

Mating in female rats induces an acute prolactin (PRL) release within 60 min and twice-daily surges of PRL throughout the first 10 days of pregnancy to maintain luteal function. Little is known about the brain mechanism whereby the vaginocervical stimulation is processed to induce PRL release. Our recent results revealed an increase in Fos expression in the arcuate nucleus (ARC) following mating in the intact estrous rat, suggesting that a neuronal network in the brain area may participate in conveying and integrating the genitosensory stimulation. To further investigate the phenotype of activated neurons in the ARC, the present study examined whether β-endorphin (β-END) and/or dopamine (DA) neurons are activated by mating, and if so, whether activation is involved in the mating-induced acute release of PRL and the establishment of the twice-daily surges of PRL. In experiment 1, proestrous rats receiving intromissions (mated group) from males or mounts without intromission (mounted group) were sacrificed along with rats taken directly from their home cage (control group) 60 min after the beginning of mating or mounting. Expression of Fos in β-END neurons and expression of fos-related antigen (FRA) in DA neurons, which were labeled by tyrosine hydroxylase (TH) antibody in the ARC were examined by double-label immunocytochemistry. In experiment 2, proestrous females with indwelling atrial catheters were mated with males. Naloxone (10 µl/min, 2 mg/10 min), an opiate antagonist, or saline was infused before, during and after mating. Blood samples were collected during the mating session and also at several times 3 days after mating. The results showed that mating induced a significant increase in the percentage of β-END/Fos colabeled neurons and a significant decrease in the number of β-END cells in all subdivisions of the ARC. In contrast, neither the percentage of FRA/TH colabeled cells nor the number of TH cells was influenced by mating. Mating induced an acute increase in PRL release in saline-treated control animals within 30 min and a subsequent diurnal surge (18.00 h) and a nocturnal surge of PRL (2.00 h) 3 days after mating. Naloxone infusion during mating blocked the mating-induced acute PRL response and the diurnal surge of PRL 3 days after mating, but affected neither the nocturnal surge of PRL nor the incidence of pregnancy. These results demonstrate that (1) β-END neurons but not DA neurons in the ARC are activated in response to mating in proestrous rats, and (2) the mating-induced activation of β-END neurons may participate in the acute response of PRL release to mating and the memory mechanism for the establishment of the diurnal PRL surge, but not the nocturnal PRL surge in early pregnancy. These results lead to a conclusion that endogenous opioid peptides may be involved in the neuronal transmission of genitosensory stimulation to induce PRL secretion.

Effect of Adrenalectomy on Mating-Induced Prolactin Surges and Pseudopregnancy in the Female Rat

“…Despite relatively frequent sampling, we did not observe overall differences between 15I and MO animals. These results corroborate previous work showing that the expression of the first mating-induced nocturnal PRL surge is delayed, and does not occur until 24–48 h post-mating [6, 23, 27, 29]. The tonically low concentrations of PRL between 6 and 8 h (01:00–07:00 h) after mating may be due to increases in dopaminergic tone, to inhibition of one or more PRL releasing factors [32, 33]and/or to circadian signals regulating the timing of PRL secretion.…”

“…The fact that animals receiving MO did not show the acute surge demonstrates that its presence is not the direct result of stress associated with testing or other sensory inputs provided by male contact other than the VCS [26]. This acute surge has been demonstrated to be unnecessary for the establishment of P/PSP [23, 29, 30]. Therefore, it does not seem likely that the neuroendocrine control of this acute surge is similar to the mechanisms regulating the bi-circadian surges.…”

Identification of Neuropeptide W as the Endogenous Ligand for Orphan G-protein-coupled Receptors GPR7 and GPR8

“…Stimulation of prolactin release was observed upon the intracerebroventricular administration of NPW. Although it is known that GPR7 is expressed in pituitary gland, where prolactin is secreted in response to physiological stimuli (13,30,31), further studies will be required to determine whether NPW activates the pituitary cells directly or indirectly by other mechanisms. To define the physiological importance of NPW in complex pathways of feeding and prolactin release, development of selective antagonists for the receptors of NPW and genetically engineered mice with a deletion of NPW or its receptor genes will be useful.…”

c-<i>fos</i> Expression in the Forebrain after Mating in the Female Rat Is Altered by Adrenalectomy

“…The ARC plays an important role in regulation of the HPA axis as well as PRL secretion, in part via β-endorphin neurons with the ARC [57]. Studies using intact estrous females showed an increase in FOS activity in β-endorphin neurons in the ARC after mating [21, 57]and Adx has been demonstrated to increase hypothalamic β-endorphin in males [60].…”

“…The ARC plays an important role in regulation of the HPA axis as well as PRL secretion, in part via β-endorphin neurons with the ARC [57]. Studies using intact estrous females showed an increase in FOS activity in β-endorphin neurons in the ARC after mating [21, 57]and Adx has been demonstrated to increase hypothalamic β-endorphin in males [60]. β-Endorphin is known to be a potent stimulator of PRL release [35, 37, 58], and endogenous opioid peptides have been shown to modulate both the proestrus and the mating-induced prolactin surges in female rats [59].…”