PRL is an anterior pituitary hormone that, along with GH and PLs, forms a family of hormones that probably resulted from the duplication of an ancestral gene. The PRLR is also a member of a larger family, known as the cytokine class-1 receptor superfamily, which currently has more than 20 different members. PRLRs or binding sites are widely distributed throughout the body. In fact, it is difficult to find a tissue that does not express any PRLR mRNA or protein. In agreement with this wide distribution of receptors is the fact that now more than 300 separate actions of PRL have been reported in various vertebrates, including effects on water and salt balance, growth and development, endocrinology and metabolism, brain and behavior, reproduction, and immune regulation and protection. Clearly, a large proportion of these actions are directly or indirectly associated with the process of reproduction, including many behavioral effects. PRL is also becoming well known as an important regulator of immune function. A number of disease states, including the growth of different forms of cancer as well as various autoimmune diseases, appear to be related to an overproduction of PRL, which may act in an endocrine, autocrine, or paracrine manner, or via an increased sensitivity to the hormone. The first step in the mechanism of action of PRL is the binding to a cell surface receptor. The ligand binds in a two-step process in which site 1 on PRL binds to one receptor molecule, after which a second receptor molecule binds to site 2 on the hormone, forming a homodimer consisting of one molecule of PRL and two molecules of receptor. The PRLR contains no intrinsic tyrosine kinase cytoplasmic domain but associates with a cytoplasmic tyrosine kinase, JAK2. Dimerization of the receptor induces tyrosine phosphorylation and activation of the JAK kinase followed by phosphorylation of the receptor. Other receptor-associated kinases of the Src family have also been shown to be activated by PRL. One major pathway of signaling involves phosphorylation of cytoplasmic State proteins, which themselves dimerize and translocate to nucleus and bind to specific promoter elements on PRL-responsive genes. In addition, the Ras/Raf/MAP kinase pathway is also activated by PRL and may be involved in the proliferative effects of the hormone. Finally, a number of other potential mediators have been identified, including IRS-1, PI-3 kinase, SHP-2, PLC gamma, PKC, and intracellular Ca2+. The technique of gene targeting in mice has been used to develop the first experimental model in which the effect of the complete absence of any lactogen or PRL-mediated effects can be studied. Heterozygous (+/-) females show almost complete failure to lactate after the first, but not subsequent, pregnancies. Homozygous (-/-) females are infertile due to multiple reproductive abnormalities, including ovulation of premeiotic oocytes, reduced fertilization of oocytes, reduced preimplantation oocyte development, lack of embryo implantation, and the absence of pseudopregnancy. Twenty per cent of the homozygous males showed delayed fertility. Other phenotypes, including effects on the immune system and bone, are currently being examined. It is clear that there are multiple actions associated with PRL. It will be important to correlate known effects with local production of PRL to differentiate classic endocrine from autocrine/paracrine effects. The fact that extrapituitary PRL can, under some circumstances, compensate for pituitary PRL raises the interesting possibility that there may be effects of PRL other than those originally observed in hypophysectomized rats. The PRLR knockout mouse model should be an interesting system by which to look for effects activated only by PRL or other lactogenic hormones. On the other hand, many of the effects reported in this review may be shared with other hormones, cytokines, or growth factors and thus will be more difficult to study. (ABSTRACT TRUNCATED)

Prolactin (PRL) and Its Receptor: Actions, Signal Transduction Pathways and Phenotypes Observed in PRL Receptor Knockout Mice

The right ovary and oviduct are present in embryonic stages of all birds, but the distribution of primordial germ cells to the ovaries of the chicken becomes asymmetrical by day 4 of incubation, and by day 10 regression of the right oviduct begins. The reproductive system of birds (Galliformes) consists of a single left ovary and its oviduct, although on occasion a functional right ovary and oviduct may be present. Among the falconiformes and in the brown kiwi, both left and right gonads and associated oviducts are commonly functional, although the ovaries may be asymmetrical in size; in sparrows and pigeons, about 5% of specimens have two developed ovaries (see Romanoff and Romanoff, 1949; Kinsky, 1971).

Reproduction in the Female

Publisher Summary This chapter describes the different aspects of the physiology of smolting salmonids. Many salmonids—the fish of the genera, Oncorhynchus , Salmo , and Salvelinus —are anadromous and undergo a distinct transformation prior to seaward migration. Several morphological and physiological changes occur during smolting. Silvering is because of the synthesis of two purines–guanine and hypoxanthine. The needle-like crystals of these substances are deposited in two distinct skin layers: one directly beneath the scales and the other deep in the dermis adjacent to the muscles. The salmonids, as many other temperate-zone animals, have a seasonally changing physiology that is manifested in the cycles of growth, precisely timed migrations, and the seasons of reproduction geared to the most favorable seasons for the birth and development of the young. There is a circannual rhythm of physiological changes associated with the parr–smolt transformation. After juvenile salmon reach a certain critical size, they become smolts with a capacity to hypoosmoregulate and grow in seawater and behavioral changes result in a downstream migration.

4 The Physiology of Smolting Salmonids

The time in spring when a male kestrel rapidly increases his daily hunting time and his hunting yield, and thereby the amount of food delivered to the female, determines the date when she lays the first egg. Food experiments in free-living and captive kestrels gave a significant advance in laying date. Clutch size, which decreases with progressive laying date, did not change independent of date in response to food manipulation. These effects are in agreement with most other feeding experiments. Photoperiod experiments in kestrels advanced the reproductive cycle in constant long days, and a similar seasonal decline in clutch size was found. It seems that there is an internally preprogrammed decrease in clutch size within an annual "reproductive window". A proximate control model for the seasonal decline of clutch size is proposed, modified from an earlier model by HAFTORN (1985). This incorporates an increasing tendency to incubate the first eggs with progression of the season, an egg contact-incubation positive feedback loop, and the resorption of further follicles in the ovary when the laying female incubates 50% of the time. This follicle resorption fixes the clutch size ca. four days before the last egg is laid. the 50% incubation level is reached earlier in late females and consequently resorption starts earlier and the resulting clutch is smaller than in early females. Experiments in kestrels with removal and addition of eggs, in combination with measurements of incubation behaviour are discussed in relation to the model. Plasma prolactin data of female kestrels show that this hormone is a serious candidate for a physiological component relaying time of year in our model for clutch size regulation.

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Family planning in the kestrel (Falco tinnunculus): the ultimate control of covariation of laying date and clutch size

Chapter 4 – HORMONAL CORRELATES OF BEHAVIOR

The concentrations of prolactin, LH, progesterone and GH were measured in the blood of broody bantam hens. The concentration of prolactin was at its highest when the birds began to incubate their eggs and in six out of nine hens it tended to remain raised until the eggs hatched. The increase in the concentration of prolactin was small: in incubating hens it was only 23% higher than in hens caring for their young and 14% higher than in laying hens (P less than 0.05 for both comparisons). The concentration of GH tended to be depressed in hens caring for young but otherwise was not related to reproductive activity. The concentrations of LH and progesterone decreased at the onset of incubation and remained depressed while the hens sat on their eggs (P less than 0.001) for both comparisons). After the chicks hatched, the level of LH began to increase slowly whereas the level of progesterone remained low. The hens stopped showing broody behaviour between 4 and 10 weeks after the chicks had hatched; this corresponded to the time when the concentration of LH had increased to values found in laying hens. These observations provide some evidence that prolactin secretion increases at the onset of incubation and support the view that the hormone is not secreted at an increased rate while hens are caring for their young.

Variations in concentrations of prolactin, luteinizing hormone, growth hormone and progesterone in the plasma of broody bantams (Gallus domesticus)

The time spent each day on the nest and the rate of formation of the brood patch before the onset of incubation were measured in bantams (Gallus domesticus) and related to changes in the concentrations of plasma LH and prolactin. The hens spent progressively more time on the nest in the 5 days before the onset of incubation so that by the first day of incubation they were spending more than 90% of their time in this way. The concentration of plasma prolactin increased while that of LH fell on successive days before the onset of incubation: the increase in plasma prolactin preceded the fall in plasma LH by 2 days. The formation of the brood patch closely followed the increase in the concentration of plasma prolactin. In four out of five bantams the increase in nesting behavior was preceded by an increase in the secretion of prolactin. An injection of chicken prolactin antiserum into bantams incubating eggs resulted in a significant (P less than 0.05) increase in the plasma concentration of LH. The observations suggest that, in the bantam, the onset of incubation is initiated by an increase in the secretion of prolactin which also suppresses the secretion of LH.

The possible role of prolactin in the regulation of nesting behaviour and the secretion of luteinizing hormone in broody bantams

The effects of thyrotropin-releasing hormone (TRH) on growth hormone (GH) and prolactin (Prl) secretion have been investigated in vitro and in vivo in domestic fowl. In both conscious and anaesthetized immature chickens the administration (i.v.) of TRH (2.5 and 25 microgram/kg) significantly increased the concentration of plasma GH. The simultaneous administration of somatostatin (GHRIH), 2.5 microgram/kg, to conscious birds significantly reduced the magnitude of the GH response to TRH treatment, but had no effect on the basal levels of plasma GH. The repeated injection of TRH (10 microgram/kg) every 20 min over a 100-min period failed to maintain the concentration of plasma GH at a high level. Prl secretion was not stimulated in any of these experiments, and in anaesthetized birds TRH (2.5 and 25 microgram/kg) treatment was followed by a depression in the level of plasma Prl. The effects of TRH and GHRIH on GH secretion by an in vitro dispersed pituitary cell suspension system were very similar to the in vivo studies. TRH stimulated Prl release in vitro, in contrast to the in vivo studies, and the response was dose related. GHRIH had no effect on the basal release of Prl in vitro but significantly inhibited the response to TRH treatment.

The Effect of Thyrotropin-Releasing Hormone (TRH) and Somatostatin (GHRIH) on Growth Hormone and Prolactin Secretion in vitro and in vivo in the Domestic Fowl (Gallus domesticus)

1. Plasma growth hormone (GH) and prolactin concentrations were measured between 1 and 24 weeks of age in both sexes of a laying strain of chickens and from 1 to 9 weeks of age in broiler cockerels. 2. GH and prolactin concentrations were highest in young birds and higher in males than in females. 3. In both sexes GH and prolactin concentrations were correlated inversely with age and body weight and positively with relative weight gain. 4. Differences in growth rate between broilers and layers were related to differences in blood GH concentrations. 5. Water deprivation for periods of 6, 12, 18 or 24 h increased plasma prolactin markedly but did not affect GH secretion significantly.

Growth hormone and prolactin secretion in growing domestic fowl: Influence of sex and breed

The concentrations of both GH and prolactin in the circulation of the domestic fowl have been determined after various treatments known to affect carbohydrate metabolism. Fasting decreased the level of glucose, stimulated the secretion of GH and inhibited the secretion of prolactin. Administration of insulin significantly depressed the level of GH in the plasma of normal or fasted birds and also in chickens which had received simultaneous injections of glucose or 2-deoxy-D-glucose. No consistent effect of insulin on the secretion of prolactin was observed. Hyperglycaemia subsequent to administration of glucose had no effect on the levels of either GH or prolactin. Glucagon-induced hyperglycaemia suppressed the level of GH in the plasma and stimulated that of prolactin.

Arthur Chadwick

Papers

Variations in concentrations of prolactin, luteinizing hormone, growth hormone and progesterone in the plasma of broody bantams (Gallus domesticus)

The possible role of prolactin in the regulation of nesting behaviour and the secretion of luteinizing hormone in broody bantams

The Effect of Thyrotropin-Releasing Hormone (TRH) and Somatostatin (GHRIH) on Growth Hormone and Prolactin Secretion in vitro and in vivo in the Domestic Fowl (Gallus domesticus)

Growth hormone and prolactin secretion in growing domestic fowl: Influence of sex and breed

Influence of fasting, glucose and insulin on the levels of growth hormone and prolactin in the plasma of the domestic fowl (Gallus domesticus).