Prolactin receptors

The growth hormone also binds to the prolactin receptor... 

The prolactin receptor, PER, which regulates milk production in mammals, belongs to the same receptor class as the growth hormone receptor. In addition to binding the hormone prolactin, PER also binds and is activated by growth hormone. The extracellular domain of PER forms a very stable 1 1 complex with growth hormone in solution this complex has been crystallized and its structure determined (Figure 13.21). We shall compare this structure with the 1 2 complex of the same hormone with GHR. 

Figure 13.22 Hormone-receptor interactions involving the domain-domain linker region in the receptor, (a) Interactions between the growth hormone (red) and the growth hormone receptor (blue) linker region. Glu 127 of the receptor forms a salt bridge to Arg 167 in the hormone, (b) The same interaction area in the growth hormone (red)-prolactin receptor (green) complex. The displacement of the linker region due to differences in the domain orientations have brought Asp 124 in the prolactin receptor into contact with Arg 167 of the hormone. (Adapted from W. Somers et al.. Nature 372 478-481, 1994.)...

Prolactin is peptide hormone secreted by the pituitary gland. It acts on prolactin receptors in breast tissue where it stimulates production of casein and lactalbu-min. It also acts on the testes and ovaries to inhibit the effects of gonadotrophins. Since the secretion of prolactin is under tonic dopaminergic inhibition by the hypothalamus, dopamine D2-receptor antagonists... 

The pituitary, as well as the hypothalamic hormones, also contribute to VN development. A transient prolactin receptor (PRLR) is expressed in the late foetal rat. At El8, there is positive staining for this binding protein along the lumenal border the reaction is restricted to the medial (sensory) zone [Freemark et al, Fig. 6(d), 1996]. These sites possibly function in the detection of endogenous lactogenic ligands such as PL-I and PL-II. The VNORs also occupy microvillous sites in this area, but the precise developmental role of PRLR in the early AOS is unknown. The modulatory influence of prolactin is well established after puberty in mammals as a reproductive determinant (Chap. 5). In a more central role, it acts on the EOG recorded from the accessory area of the bulb in newts (Toyoda, 2000). 

In addition to the classical stress hormones already reviewed, several other hormones are augmented in response to stress. Stress-induced prolactin release is one of the most frequently studied examples. There is no doubt about the causal relationship between stress and increased pituitary prolactin release, but the biological meaning is much less clear (G2). This phylogenetically old hormone has been shown to have more than 85 different functions in all vertebrate species. However, besides its role in the induction of maternal lactogenesis, the physiological importance of prolactin is at present not fully established. Experimental and clinical evidence supports the view that prolactin is also an immunoregulating hormone (M44, R18). Prolactin receptors are present on human T and B lymphocytes (R18), and T lymphocytes depend on prolactin for maintenance of immunocompetence (B19). In addition, it has been shown that prolactin is able to influence the devel-... 

Placental lactogen Prolactin receptor Extracellular domain Monomeric 1 2... 

Cahoreau C, Gamier L, Djiane J, Devauchelle G, Cerutti M (1994) Evidence for N-glycosylation and ubiquitination of the prolactin receptor expressed in a bacu-lovirus-insect cell system. FEBS Lett 350 230-234 Caplan S, Green R, Rocco J, Kurjan J (1991) Glycosylation and structure of the yeast MF a 1 a-factor precursor is important for effident transport through the secretory pathway. J Bacteriol 173 627-35... 

Fig. 3A, B Neuropeptide effects on anxiety-related behavioiu. A The oxytocin receptor antagonist (black bars) administered intracerebroventricularly (i.c.v.) increased indices of anxiety-related behaviour in pregnant rats as measured on the elevated plus maze. Entries into the closed arms indicate unchanged locomotor activity. B Prolactin is an anxiolytic neuropeptide in female rats as revealed by i.c.v. administration of synthetic prolactin (grey and black bars represent two different doses) and by antisense targeting of the prolactin receptor (R). Vehicle (white bars) vs mixed bases (grey bars) and antisense oligodeoxynu-cleotide (black bars). p<0.05 vs vehicle (white bars). (Adapted from Nemnann et al. 2000) and Torner et al. 2001)...

Hexane extract, in Ghinese hamster ovary cells overexpressing the prolactin receptor at a concentration of 30 pg/mL, was active . 

The lipidosterolic extract, in Chinese hamster ovary cells, reduced the basal activity of a K channel and of protein kinase (PK) C. Pretreatment of the cells with the extract for 6-36 hours abolished the effects of prolactin on Ca 3 K conductance and PKC. The results indicated that the extract can block prolactin-induced prostate growth by inhibiting several steps of prolactin receptor signal transduction . 

Chinese hamster ovary cells overexpressing the prolactin receptor, was active . Protein synthesis stimulation. Sterol fraction of the extract, in cell culture at a concentration of 25 (xg/mL, produced weak activity on CA-LNCAP. A concentration of 50 (xg/mL was active on CA-PC3 h PSA production inhibition. Ethanol (70%) extract of PC-SPES (a Chinese herb combination of chrysanthemum, dyers woad, licorice, reishi, san-qi ginseng, rabdosia, saw palmetto, and baikal skullcap), in cultured prostate cancer cell line at variable doses for 24 hours, produced a significant effect in supressing cell growth in all the cell lines h... 

SR021 Vacher, P., N. Prevarskaya, R. Skryma, M. C. Audy, A. M. Vacher, M. F. Odessa, and B. Dufy. The lipidosterolic extract from Serenoa repens interferes with prolactin receptor signal transduction. J Biomed Sci 1995 2(4) 357-365. 

Knockout of the prolactin receptor, rather than knockout of prolactin, is necessary to explore the role of the hormone and its receptor in maternal behavior because several molecules other than prolactin, including growth hormone (GH) and placental lactogens, may stimulate the prolactin receptor. Disruption of the prolactin receptor gene in a mouse model has allowed for assessment of phenotypes associated with partial and complete prolactin receptor deficits (Goffin et ah, 1999). Prolactin receptor knockout mice have severe reproductive deficits. Heterozygous mothers (receptor —/+) were also unable to lactate (Bridges, 1998). 

Lucas, B.K., Ormandy, C.J., Binart, N., Bridges, R.S., and Kelly, P.A. (1998) Null mutation of the prolactin receptor gene produces a defect in maternal behavior. Endocrinology 139 4102-4107. 

Murphy LC, Murphy LJ, Tsuyuki D, Duckworth ML, Shiu RP. 1988. Cloning and characterization of a cDNA encoding a highly conserved, putative calcium binding protein, identified by an anti-prolactin receptor antiserum. J Biol Chem 263(5) 2397—2401. 

Roky R, Paut-Pagano L, Goffin V, Kitahama K, Valatx JL, Kelly PA, Jouvet M. Distribution of prolactin receptors in the rat forebrain, immunohistochemical study. Neuroendocrinology 1996 63 422 -29. 

Prolactin receptors from a number of other tissues, including rat and mouse liver [30,31], have been solubilized using various detergents and then partially characterized using gel filtration. The apparent Mx found appears to depend on the type of detergent used for solubilization, and in one study a prolactin-binding subunit ... 

Fig. 4. Antibodies to the prolactin receptor block the actions of the hormone on casein synthesis in rabbit mammary tissue explants. CS, control serum AS, antiserum to receptor P, prolactin. Data from Ref. 45.

---