Regulation of Prolactin Secretion: Dopamine is the Prolactin-release Inhibiting Factor (PIF), but also Plays a Role as a Releasing Factor (PRF)

Shin, Seon H.,Song, Jin-Hyang,Ross, Gregory M. The Korean Society for Integrative Biology 1999 Korean journal of biological sciences Vol.3 No.2

Many in-depth reviews related to regulations of prolactin secretion are available. We will, therefore, focus on controversial aspects using personal opinion in this review. The neuroendocrine control of prolactin secretion from the anterior pituitary gland involves multiple factors including prolactin-release inhibiting factor (PIF) and prolactin releasing factor (PRF). The PIF exerts a tonic inhibitory control in the physiological conditions. The PIF should be able to effectively inhibit prolactin release or a lifetime, but the inhibitory action of dopamine cannot be sustained for a long period of time. Perifusion of a high concentration of dopamine (l ,000 nM) could not sustain inhibitory action on prolactin release but when a small amount of ascorbic acid (0.1 mM) is added in a low concentration of dopamine (3 nM) solution, prolactin release was inhibited for a long period. Ascorbate is essential for dopamine action to inhibit prolactin release. We have, therefore, concluded that the PIF is dopamine plus ascorbate. The major transduction system for dopamine to inhibit prolactin release is the adenylyl cyclase system. Dopamine decreases cyclic AMP concentration by inhibiting adenylyl cyclase, and cyclic AMP stimulates prolactin release. However, the inhibitory mechanism of dopamine on prolactin release is much more complex than simple inhibition of CAMP production. The dopamine not only inhibits cyclic AMP synthesis but also inhibits prolactin release by acting on a link(s) after the CAMP event in a chain reaction for inhibiting prolactin release. Low concentrations of dopamine stimulate prolactin release. Lactotropes are made of several different subtypes of cells and several different dopamine receptors are found in pituitary. The inhibitory and stimulatory actions induced by dopamine can be generated by different subtype of receptors. The GH$_4$ZR$_7$</tEX> cells express only the short isoform (D$_{2s}$) of the dopamine receptor, as a result of transfecting the D$_{2s}$ receptors into GH$_4$C$_1$ cells which do not express any dopamine receptors. When dopamine stimulates or inhibits prolactin release in GH$_4$ZR$_7$</tEX> cells, it is clear that the dopamine should act on dopamine D$_{2s}$ receptors since there is no other dopamine receptor in the GH$_4$ZR$_7$</tEX>. Dopamine is able to stimulate prolactin release in a relatively low concentration while it inhibits in a high concentration in GH$_4$ZR$_7$</tEX>. These observations indicate that the dopamine D$_2$ receptor can activate stimulatory and/or inhibitory transduction system depending upon dopamine concentrations.

Prolactin Monomeric Polyethylene Glycol Measurement Method and Study of Reference Value Verification

Dong Hyuk Ha,Hwa-Jin Ryu,Hyun-Su Cho,Sun-Young Shin 대한핵의학기술학회 2023 핵의학 기술 Vol.27 No.2

Purpose: Prolactin in the blood is separated into three types, and over 90% of prolactin presents as a double monomer (23 KDa). Rarely, it can exist in the size of big prolactin (150 KDa), which is called macroprolactin and is known as an autoantibody complex. When macroprolactin accounts for more than 60% of prolactin in the blood, it is called macroprolactinemia. The presence of such macroprolactin was first reported in a patient with hyperprolactinemia but without typical symptoms. Macroprolactinemia is emerging as an important cause of idiopathic hyperprolactinemia. The polyethylene glycol (PEG) precipitation method using the property of precipitating large-molecular-weight proteins is simple and recently has been widely used as a screening test. The results are in good agreement with the results of gel chromatography. The purpose of this study was to confirm the measurement method and reference value verification of monomeric prolactin in blood prolactin using the PEG precipitation method. Materials and Methods: For 40 examinees who visited the Gangnam Center of Seoul National University Hospital in 2021, the prolactin level was verified using radioimmunoassay (RIA). For macroprolactinemia PEG precipitation method, 25% PEG (molecular weight 6000kDa) solution and serum were mixed in equal amounts in a test tube, then left at room temperature for 20 minutes and centrifuged at 4℃ for 30 minutes (1500g). The prolactin level was measured in the supernatant. Results : After confirming that more than 90% of the 40 tested samples within the reference range <25 ng/mL, the same value as the reference value for prolactin was applied. Since the concentration of monomeric prolactin in serum from which macroprolactin has been removed from blood is diluted 1:1 with PEG, our laboratory is currently reporting the result by multiplying the result by a dilution factor of 2. Conclusion: Radioimmunoassay using PEG precipitation method using the property of precipitating large molecular weight proteins is simple and effective for quantitative measurement of monomeric prolactin in blood prolactin.

산란계의 뇌하수체 세포배양에서 Prolactin의 생성에 관계하는 Protein Kinase C의 역할

선상수 한국가금학회 1996 韓國家禽學會誌 Vol.23 No.3

A series of experiments were conducted to investigate the role of protein kinase C (PKC) as a second messenger in vasoactive intestinal peptide (VIP) mediated prolactin secretion. Primary pituitary cells (106 cells/treatment) were separated from laying hens and incubated in M-199 with 5% chicken serum and 5% fetal calf serum. The VIP(0.1 $\pi$M) treatment enhanced prolactin Secretion into media upto 9-fold during 48-h incubation. The phorbol 12-myristate 13-acetate (PMA), a PKG agonist, increased prolactin secretion upto 2-fold at 0.1 nM PMA (P<0.01), and the prolactin secretion was not significantly higher than this concentration. Staurosporine (ST; 1.0$\pi$M) a PKC antagonist, decreased by 70% of 0.1 $\pi$M VIP-stimulated prolactin secretion and by 48% of 10 ${\mu}$M PMA-stimulated prolactin secretion (P<0.01). However, pituitary cell prolactin content did not differ in any treatment (P>0.05). In conclusion, these results indicate that the PKC second messenger system is involved in VIP-stimulated prolactin release in chicken primary pituitary cell culture.

황체기 결함이 있는 불임환자에서 클로미펜 투여 여부에 따른 자궁내막 내의 Prolactin의 발현 양상의 비교 연구

고승희,황정혜,심의섭,고재환,김용봉,장세진,Goh, Seung-Hee,Hwang, Jung-Hye,Sim, Ey-Sub,Koh, Jae-Whoan,Kim, Yong-Bong,Jang, Se-Jin 대한생식의학회 2003 Clinical and Experimental Reproductive Medicine Vol.30 No.1

Objective : Clomiphene citrate is one of the most commonly used drugs in the treatment of infertility, but the pregnancy rate achieved with clomiphene citrate is significantly lower than the ovulation rate due to its antiestrogenic effect on the endometrium. Endometrial prolactin is considered to be a marker and an inducer of predecidualization that is characteristic of secretory endometrium. The purpose of this study was to evaluate the association of clomiphene citrate and unsatisfactory endometrial differentiation to secretory endometrium by examining the endometrial expression of prolactin in clomiphene citratetreated infertile women with luteal phase defect. Methods : The endometrial samples from infertile women with luteal phase defect (n=27) were examined. Five cases during secretory phase and six cases during proliferative phase were obtained by biopsy. Sixteen cases were obtained by biopsy during secretory phase after clomiphene citrate treatment. By immunohistochemical staining for prolactin, all obtained endometrial tissues were examined. The differences in the endometrial expression of prolactin were evaluated between proliferative phase and secretory phase, and between clomiphene citrate treated group and no treatment group during secretory phase. Results: The staining of endometrial prolactin was significantly more intense in the glandular epithelial cells and stromal cells in the secretory endometrium than in the proliferative endometrium. The glandular expression of prolactin in the secretory endometrium was not significantly different between the clomiphene citrate-treated group and no treatment group (p=0.719), but the staining of prolactin in the stromal cells was significantly less intense in the clomiphene citrate-treated group than no treatment group (p=0.019). Conclusion: In this investigation, we demonstrated that the endometrial stromal expression of prolactin in the secretory phase was significantly lower in the clomiphene citrate-treated group campared with no treatment group in infertile women with luteal phase defect. And our finding suggests that clomiphene citrate may have an adverse effect on the endometrial predecidualization in infertile women.

Buspirone-induced Prolactin Secretion in Man is Not $5-HT_{1A}$ Receptor Mediated: Effect of Pindolol Pretreatment

Lee, Hong-Shick,Nash, J. Frank,Meltzer, Herbert Y. The Korean Society of Pharmacology 1992 대한약리학잡지 Vol.28 No.1

Nonbenzodiazepine계 항불안제인 buspirone을 이용하여 건강한 8명의 남자를 대상으로 prolactin과 cortisol분비를 측정하였다. Buspirone는 $Dopamine_2$ 수용체 antagonist 성질 뿐 아니라 $5-HT_{1A}$ partial agonist 효과가 있는 것으로 보고되고 있다. Buspirone 30mg 경구투여시 혈청 prolactin 농도는 유의한 증가를 보였으나 혈청 cortisol 농도의 변화는 차이가 없었다. beta adrenoreceptor antagonist이면서 $5-HT_{1A}$ 수용체 antagonist로 알려진 pindolol (30mg)을 경구 투여한 결과 기초 혈청 prolactin이나 cortisol 농도는 유의한 차이가 없었다. Pinodlol을 전처치한 경우 buspirone-induced prolaction 분비의 유의한 억제효과는 없었다. 이상의 성적은 buspirone-induced prolactin 분비증가는 아마도 $5-HT_{1A}$ 수용체 활성과 관련되지 않음을 시사하는 것으로 사료된다. The effect of the nonbenzodiazepine anxiolytic, buspirone $(Buspar^R)$, a serotonin $(5-HT)_{1A}$ partial agonist, which also has dopamine $(DA)_2$ receptor antagonist properties, on prolactin and cortisol secretion was examined in eight normal male volunteers. The oral administration of buspirone (30 mg) significantly increased plasma prolactin concentrations but did not significantly increase plasma cortisol concentrations in this study. The oral administration of pindolol (30 mg), a beta adrenoceptor antagonist which is also a $5-HT_{1A}$ receptor antagonist, had no significant effect on basal prolactin or cortisol levels. Moreover, pretreatment with pindolol did not significantly inhibit the buspirone-induced increase in prolactin secretion. These preliminary data are suggestive that buspirone-induced prolactin secretion is not mediated via $5-HT_{1A}$ receptor activation.

Buspirone-induced Prolaction 분비와 5-HT_1A 수용체: Pindolol 전처치 효과

이홍식(Hong Shick Lee),J. Frank Nash,Herbert Y. Meltzer 대한약리학회 1992 대한약리학잡지 Vol.28 No.1

Nonbenzodiazepine계 항불안제인 buspirone을 이용하여 건강한 8명의 남자를 대상으로 prolactin과 cortisol분비를 측정하였다. Buspirone는 DopaminE₂ 수용체 antagonist 성질 뿐 아니라 5-HT_1A partial agonist 효과가 있는 것으로 보고되고 있다. Buspirone 30mg 경구투여시 혈청 prolactin 농도는 유의한 증가를 보였으나 혈청 cortisol 농도의 변화는 차이가 없었다. beta adrenoreceptor antagonist이면서 5-HT_1A 수용체 antagonist로 알려진 pindolol (30mg)을 경구 투여한 결과 기초 혈청 prolactin이나 cortisol 농도는 유의한 차이가 없었다. Pinodlol을 전처치한 경우 buspirone-induced prolaction 분비의 유의한 억제효과는 없었다. 이상의 성적은 buspirone-induced prolactin 분비증가는 아마도 5-HT_1A 수용체 활성과 관련되지 않음을 시사하는 것으로 사료된다. The effect of the nonbenzodiazepine anxiolytic, buspirone (Buspar^R), a serotonin (5-HT)_1A partial agonist, which also has dopamine (DA)₂ receptor antagonist properties, on prolactin and cortisol secretion was examined in eight normal male volunteers. The oral administration of buspirone (30 mg) significantly increased plasma prolactin concentrations but did not significantly increase plasma cortisol concentrations in this study. The oral administration of pindolol (30mg), a beta adrenoceptor antagonist which is also a 5-HT_1A receptor antagonist, had no significant effect on basal prolactin or cortisol levels. Moreover, pretreatment with pindolol did not significantly inhibit the buspirone-induced increase in prolactin secretion. These preliminary data are suggestive that buspirone-induced prolactin secretion is not mediated via 5-HT_1A receptor activation.

姙娠中毒症 患者의 血漿內 Prolactin値에 關한 硏究

金龍鳳,金浩聖,李應洙,李鴻均 인제대학교 1989 仁濟醫學 Vol.10 No.1

姙娠中毒症의 發生機轉에 prolactin의 關與 與否를 알기 위한 目的으로 姙娠中毒症 患者 20例를 對象으로 血漿內 prolactin 濃度를 測定하고 正常 姙婦의 그것과 比較·檢討하였다. Pre-eclampsia is characterized by hypertension and generalized vasoconstriction, but its cause is still obscure. Recently a possible relation between plasma prolactin concentration and blood pressure during pregnancy has reported by some investigators. Therefore, in order to study the etiologic involvement of prolactin in pre-eclampsia, we measured the plasma concentrations of prolactin in groups of women suffered from mild and severe pre-eclampsia and compared with normal pregnant controls. The results were as follows ; 1.The mean plasma prolactin concentrations of normal pregnant controls and pre-eclampsia group were 219±67ng/ml and 255±65 ng/ml respectively, The concentration of pre-eclampsia group was higher the that of normal pregnant controls but there was no significant difference between the two. 2.The mean plasma prolactin concentrations of mild and severe pre-eclampsia groups were 236± 61 ng/ml and 268±68 ng/ml respectively. The concentration of severe pre-eclampsia group was higher than that of mild pre-eclampsia group but there was no significant difference between the two. These results suggest that other substance rather than prolactin may be involved in increasing the vascular reactivity to pressor agents in pre-eclampsia.

만성 정신분열증 환자에 있어 Clozapine 투여에 의한 비정형적 Prolactin반응

이홍식,김찬형,기선완 대한신경정신의학회 1994 신경정신의학 Vol.33 No.3

Objects : Typical antipsychotic drugs robustily increase prolactin both in rodents and in man. Unlike in rodents, Meltzer(1989) found that acutely administered clozapine did not increases serum prolactin levels in schizophrenia and his preliminary data suggested that prolactin levels might even be reduced during clozapine treatment. Methods : We investigated the serum prolactin levels in chronic schizophrenics, who were assigned to clozapine(N=28) or haloperidol(N=20) for eight weeks. Blood samples were obtained biweekly during the study period, and serum prolactin concentrations were measured by standard double-antibody radioimmunoassay. Results : The serum prolactin levels were not changed in the schizophrenic patients to whom clozapine had been administrated, otherwise marked increases in serum prolactin level were observed in the haloperidol treatment group. Conclusion : Our results suggest that clozapine differs from typical antipsychotics(e.g., haloperidol) in its failure to produce serum prolactin elevation in schizophrenic patients.

優鬱症에서 甲狀腺 Hormones와 Prolactin의 相互作用

田珍淑 大韓神經精神醫學會 1992 신경정신의학 Vol.31 No.4

The early studies on the neuroendocrine hormones which are related to the pathogenesis of depression were focused on the hypothalamic-pituitary-adrenal axis, and then on the hypothalamic-pituitary-thyroid axis. However, recently hormones other than corticosteroids and thyroid hormones are suggested to be possibly related. Most of all, prolactin is known to influence the hypothalamic-pituitary-thyroid axis and to be involved with the control of its interacion. Previously, I had reported the experience of two cases with hyperprolactinemia secondry to the hypothyroidism accompanied by depression(Cheon 1991). By expanding the subject materials, this subsidiary study was tried to evaluate whether there is statistically significant changes in the thyroid hormones and prolactin levels in many depressed patients. Using Quanticoat Radioimmunoassay Kit, the T3 and T4 levels were quantitatively measured in 42 depressed patients who visited Department of Neuropsychiatry. Dong-Eui University Medical Center from early November. 1990 till late May. 1991. They scored over 10 in BDI. 12 in HDS and 16 in CES-D. Serum TSH levels were measured using TSH IRMA [125I] Coated Tube Immunoradiometric Assay Kit(Spectra). And serum prolactin levels were measured using Allegro Prolactin Immunoassay Kit. There is no significant change in T3 and T4 levels. However, TSH levels decreased significantly (p<0.01), and prolactin levels increased significantly(P<0.005) as compared to the control values. However, correlation between prolactin and thyroid hormones couldn't be found. Furthermore, their concentrations were not correlated with age, sex and severity of depression. In conclusion, some kind of dysfunction in thyroid hormones and prolactin seemed to be involved in the pathogenesis of depression, possibly via the interaction with serotonergic and dopaminergic mechanisms.

The Effects of Prolactin and Vasopressin on the Regulation of Amniotic Fluid Volume and Its $Na^{+}$ Concentration through the Membrane Surrounding Amniotic Fluid

Kim, Dong-Wook,Kim, Sang-Jeong,Sung, Ho-Kyung The Korean Physiological Society 1995 대한생리학회지 Vol.29 No.1

The effects of prolactin and vasopressin on the regulation of amniotic fluid (AF) volume and its $Na^{+}$ concentration $([Na^{+}])$ through the membrane surrounding the AF during increase in AF volume due to fetal urination were studied. About 70% of AF volume was replaced with normal isotonic saline solution. Isotonic saline solution (0.5 ml) containing Censored and LiCl was introduced into each amniotic sac. Vasopressin (25 ng/ml) or prolactin (1 mg/ml) of AF was then injected into experimental amniotic sac. The concentrations of Congored, $Li^{+}$, and $Na^{+}$ were measured at 30 and 60 min intervals after injection. Af samples with decreased Censored concentration ([CR]) during the period of 30 - 60 min were analyzed. The percentage change of $[Na^{+}]$ and the rate of $Li^{+}$ movement during this period were calculated, and the effects of vasopressin and prolactin on them were evaluated. Fellowing results were obtained: 1. The rate of reduction of [CR] in the AF was retarded by vasopressin or prolactin injection. 2. The rate of reduction of $[Li^{+}]$ in the AF was also retarded by vasopressin or prolactin injection. 3. The rate of reduction of $[Li^{+}]$ in the AF was less retarded by vasopressin than that of [CR]. 4. $[Na^{+}]$ changed to approach to the normal level, but this was markedly retarded by prolactin injection. 5. Direction of $Li^{+}$ movement was correlated with the change in $[Na^{+}]$ but it always moved out of the amniotic sac even when the $[Na^{+}]$ increased in vasopressin injected AF. From the above results, it is suggested that vasopressin in the AF triggers the fetus to urinate, and then the membranes surrounding the AF regulate osmolarity by efflux of $Na^{+}$. We suggest that prolactin facilitates water outflow across the amniotic membrane during increase in AF volume, in contrast to a constant volume, whereas regulation of $[Na^{+}]$ is partly restricted by prolactin.