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Influence of dynorphin on estradiol- and cervical stimulation-induced prolactin surges in ovariectomized rats

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Abstract

Prolactin is an anterior pituitary hormone necessary for fertility, pregnancy maintenance, lactation, and aspects of maternal behavior. In rodents, there is a surge of prolactin on the afternoon of proestrus, and a semi-circadian pattern of prolactin surges during early pregnancy, with a diurnal and nocturnal surge every day. Both of these patterns can be replicated in ovariectomized rats. A prior study demonstrated that central antagonism of κ-opioid receptors, the target of dynorphin, largely abolished the nocturnal prolactin surge in pregnant rats. We build on this to determine whether dynorphin, perhaps from the arcuate population that co-express kisspeptin, neurokinin B, and dynorphin (KNDy neurons), also contributes to the estradiol- or cervical stimulation-induced surges in ovariectomized rats. Ovariectomized rats were treated with either estradiol or cervical stimulation to induce prolactin surge(s). Blood samples were taken around the expected surge time to determine the effect of either acute κ-opioid receptor antagonism or previous chemical ablation of the KNDy population on prolactin levels. Dynorphin antagonism does significantly disrupt the nocturnal prolactin surge, but it does not contribute to the estradiol-induced surge. Chemical ablation of KNDy neurons had opposite effects; ablation of 40 % of the KNDy neurons had no impact on the nocturnal prolactin surge, while a somewhat larger ablation significantly reduced the size of the estradiol-induced surge. We conclude that dynorphin is likely a controlling factor for the nocturnal surge induced by cervical stimulation, and that other KNDy neuron products must play a role in the estradiol-induced surge.

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Abbreviations

CS:

Cervical stimulation

DA:

Dopamine

DOPAC:

3,4-Dihydroxyphenylacetic acid

E2 :

Estradiol

EDTA:

Ethylenediaminetetraacetic acid

HPLC:

High performance liquid chromatography

KNDy:

Kisspeptin, neurokinin B, & dynorphin

KOR:

κ opioid receptor

LH:

Luteinizing hormone

nor-BNI:

Norbinaltorphimine

OVE:

Ovariectomized with estrogen replacement

OVX:

Ovariectomized

PBS:

Phospho-buffered saline

RIA:

Radioimmunoassay

TH:

Tyrosine hydroxylase

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Acknowledgments

We thank Kim Hughes for helpful discussions, Frank Johnson for the use of his microscope, Charles Badland for assistance with figure preparation, and Lique Coolen for the antibody protocol. We also thank Frank Nenninger and Jose Arias-Cristancho, for generous assistance with surgeries, animal care, and blood sampling. This work was partially supported by the National Institutes of Health grant DK-43200.

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Authors and Affiliations

  1. Program in Neuroscience and Departments of Biological Sciences, Florida State University, Tallahassee, FL, 32306, USA

    Andrea M. Stathopoulos, Cleyde V. Helena, Ruth Cristancho-Gordo & Arturo E. Gonzalez-Iglesias

  2. Program in Neuroscience and Departments of Mathematics, Florida State University, Tallahassee, FL, 32306, USA

    Richard Bertram

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  1. Andrea M. Stathopoulos
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  2. Cleyde V. Helena
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Correspondence to Richard Bertram.

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Animal procedures were approved by the Florida State University Animal Care and Use Committee.

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Stathopoulos, A.M., Helena, C.V., Cristancho-Gordo, R. et al. Influence of dynorphin on estradiol- and cervical stimulation-induced prolactin surges in ovariectomized rats. Endocrine 53, 585–594 (2016). https://doi.org/10.1007/s12020-016-0938-1

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