2892 PART 12 Endocrinology and Metabolism

contiguous to vascular and neurologic structures, including the cavernous sinuses, cranial nerves, and optic chiasm. Thus, expanding intrasellar pathologic processes may have significant central mass effects in

addition to their endocrinologic impact.

Hypothalamic neural cells synthesize specific releasing and inhibiting

hormones that are secreted directly into the portal vessels of the pituitary

stalk. Blood supply of the pituitary gland comes from the superior and

inferior hypophyseal arteries (Fig. 378-2). The hypothalamic-pituitary

portal plexus provides the major blood source for the anterior pituitary,

allowing reliable transmission of hypothalamic peptide pulses without

significant systemic dilution; consequently, anterior pituitary cells are

exposed to specific releasing or inhibiting factors and in turn release

their respective hormones as discrete pulses into the systemic circulation (Fig. 378-3).

The posterior pituitary is supplied by the inferior hypophyseal arteries. In contrast to the anterior pituitary, the posterior lobe is directly

innervated by hypothalamic neurons (supraopticohypophyseal and

tuberohypophyseal nerve tracts) via the pituitary stalk (Chap. 381).

Thus, posterior pituitary production of vasopressin (antidiuretic hormone [ADH]) and oxytocin is particularly sensitive to neuronal damage by lesions that affect the pituitary stalk or hypothalamus.

■ PITUITARY DEVELOPMENT

The embryonic differentiation and maturation of anterior pituitary cells

have been elucidated in considerable detail. Pituitary development from

Rathke’s pouch involves a complex interplay of lineage-specific transcription factors expressed in pluripotent Sox2-expressing precursor

cells and gradients of locally produced growth factors (Table 378-1).

The transcription factor Prop-1 induces pituitary development of Pit-1-

specific lineages as well as gonadotropes. The transcription factor Pit-1

determines cell-specific expression of GH, PRL, and TSH in somatotropes, lactotropes, and thyrotropes. Expression of high levels of estrogen receptors in cells that contain Pit-1 favors PRL expression, whereas

thyrotrope embryonic factor (TEF) induces TSH expression. Pit-1

binds to GH, PRL, and TSH gene regulatory elements, providing a

mechanism for determining specific pituitary hormone phenotypic stability. Gonadotrope cell development is further defined by the cell-specific expression of the nuclear receptors steroidogenic factor (SF-1)

and dosage-sensitive sex reversal, adrenal hypoplasia critical region,

on chromosome X, gene 1 (DAX-1). Development of corticotrope

cells, which express the proopiomelanocortin (POMC) gene, requires

the T-Pit transcription factor. Abnormalities of pituitary development

can be caused by inherited mutations of developmental transcription

TABLE 378-1 Anterior Pituitary Hormone Expression and Regulation

CELL CORTICOTROPE SOMATOTROPE LACTOTROPE THYROTROPE GONADOTROPE

Tissue-specific

transcription factor

T-Pit Prop-1, Pit-1 Prop-1, Pit-1 Prop-1, Pit-1, TEF SF-1, DAX-1

Fetal appearance 6 weeks 8 weeks 12 weeks 12 weeks 12 weeks

Hormone POMC GH PRL TSH FSH, LH

Protein Polypeptide Polypeptide Polypeptide Glycoprotein α, β

subunits

Glycoprotein α, β

subunits

Amino acids 266 (ACTH 1–39) 191 198 211 210, 204

Stimulators CRH, AVP, gp-130

cytokines

GHRH, ghrelin Estrogen, TRH, VIP TRH GnRH, activins, estrogen

Inhibitors Glucocorticoids Somatostatin, IGF-1 Dopamine T3

, T4

, dopamine,

somatostatin,

glucocorticoids

Sex steroids, inhibin

Target gland Adrenal Liver, bone, other tissues Breast, other tissues Thyroid Ovary, testis

Trophic effect Steroid production IGF-1 production,

growth induction, insulin

antagonism

Milk production T4

 synthesis and secretion Sex steroid production,

follicle growth, germ cell

maturation

Normal range ACTH, 4–22 pg/L <0.5 μg/La M <15 μg/L; F <20 μg/L 0.1–5 mU/L M, 5–20 IU/L; F (basal),

5–20 IU/L

a

Hormone secretion integrated over 24 h.

Abbreviations: F, female; M, male. For other abbreviations, see text.

Source: Adapted with permission from Melmed S: Hypothalmic-pituitary regulation, in P Conn (ed): Conn’s Translational Neuroscience. San Diego, CA: Elsevier; 2017.

factors including Pit-1, Prop-1, SF-1, DAX-1, and T-Pit, resulting in

selective or combined pituitary hormone deficit syndromes.

ANTERIOR PITUITARY HORMONES

Each anterior pituitary hormone is under unique control, and

each exhibits highly specific normal and dysregulated secretory

characteristics.

■ PROLACTIN

Synthesis PRL consists of 198 amino acids and has a molecular

mass of 21,500 kDa; it is weakly homologous to GH and human placental lactogen (hPL), reflecting the duplication and divergence of a

common GH-PRL-hPL precursor gene. PRL is synthesized in lactotropes, which constitute ~20% of anterior pituitary cells. Lactotropes

and somatotropes are derived from a common precursor cell that may

give rise to a tumor that secretes both PRL and GH. Marked lactotrope

cell hyperplasia develops during pregnancy and the first few months of

lactation. These transient functional changes in the lactotrope population are induced by estrogen to increase PRL production.

Secretion Normal adult serum PRL levels are about 10–25 μg/L

in women and 10–20 μg/L in men. PRL secretion is pulsatile, with

the highest secretory peaks occurring during non–rapid eye movement (non-REM) sleep. Peak serum PRL levels (up to 30 μg/L) occur

between 4:00 and 6:00 a.m. The circulating half-life of PRL is ~50 min.

PRL is unique among the pituitary hormones in that the predominant hypothalamic control mechanism is inhibitory, reflecting tonic

dopamine-mediated suppression of PRL release. This regulatory pathway accounts for the spontaneous PRL hypersecretion that occurs with

pituitary stalk section, often a consequence of head trauma or compressive mass lesions at the skull base. Pituitary dopamine type 2 (D2

)

receptors mediate inhibition of PRL synthesis and secretion. Targeted

disruption (gene knockout) of the murine D2

 receptor in mice results in

hyperprolactinemia and lactotrope proliferation. As discussed below,

dopamine agonists play a central role in the management of hyperprolactinemic disorders.

Thyrotropin-releasing hormone (TRH) (pyro Glu-His-Pro-NH2

) is a

hypothalamic tripeptide that elicits PRL release within 15–30 min after

intravenous injection. TRH primarily regulates TSH, and the physiologic relevance of TRH for PRL regulation is unclear (Chap. 382).

Serum PRL levels rise transiently after exercise, meals, sexual

intercourse, minor surgical procedures, general anesthesia, chest wall

injury, acute myocardial infarction, and other forms of acute stress.

2893Physiology of Anterior Pituitary Hormones CHAPTER 378

Hypothalamus

Pituitary

Cortisol

ACTH

PRL

IGF-1

Target

organs

+

+

+

+

+ +

+

+

–

–

– – – +

Adrenal

glands

Lactation

Liver

Chondrocytes

Linear and

organ growth

Thyroid

glands

Testes

Ovaries

Cell homeostasis

and function

T4/T3

Thermogenesis

metabolism

Testosterone

Inhibin

Spermatogenesis

Secondary sex

characteristics

Estradiol

Progesterone

Inhibin

Ovulation

Secondary sex

characteristics

GnRH

TRH

CRH

SRIF

+

TSH

LH

FSH

Dopamine

GHRH

GH

FIGURE 378-1 Diagram of pituitary axes. Hypothalamic hormones regulate

anterior pituitary trophic hormones that in turn determine target gland secretion.

Peripheral hormones feed back to regulate hypothalamic and pituitary hormones.

For abbreviations, see text.

LH mlU/mL GnRH pg/mL

GnRH pulses

LH pulses

FIGURE 378-3 Hypothalamic gonadotropin-releasing hormone (GnRH) pulses

induce secretory pulses of luteinizing hormone (LH).

Neuroendocrine

cell nuclei

Third ventricle

Hypothalamus

Stalk

Superior

hypophyseal

artery

Long portal

vessels

Trophic

hormone

secreting

cells

Short portal

vessel

Inferior

hypophyseal

artery

Anterior

pituitary

Hormone

secretion

Posterior

pituitary

FIGURE 378-2 Diagram of hypothalamic-pituitary vasculature. The hypothalamic

nuclei produce hormones that traverse the portal system and impinge on anterior

pituitary cells to regulate pituitary hormone secretion. Posterior pituitary hormones

are derived from direct neural extensions.

PRL levels increase markedly (about tenfold) during pregnancy and

decline rapidly within 2 weeks of parturition. If breast-feeding is initiated, basal PRL levels remain elevated; suckling stimulates transient

reflex increases in PRL levels that last for ~30–45 min. Breast suckling

activates afferent neural pathways in the hypothalamus that induce

PRL release. With time, suckling-induced responses diminish and

interfeeding PRL levels return to normal.

Action The PRL receptor is a member of the type I cytokine receptor family that also includes GH and interleukin (IL) 6 receptors. Ligand binding induces receptor dimerization and intracellular signaling

by Janus kinase (JAK), which stimulates translocation of the signal

transduction and activators of transcription (STAT) family to activate

target genes. Mutations of the PRL receptor result in PRL insensitivity,

hyperprolactinemia, and oligomenorrhea. When homozygous, PRL

receptor mutations cause agalactia, demonstrating that PRL action

is necessary for lactation. In the breast, the lobuloalveolar epithelium proliferates in response to PRL, placental lactogens, estrogen,

progesterone, and local paracrine growth factors, including insulin-like

growth factor 1 (IGF-1).

PRL acts to induce and maintain lactation and to suppress both

reproductive function and sexual drive. These functions are geared

toward ensuring that maternal lactation is sustained and not interrupted by pregnancy. PRL inhibits reproductive function by suppressing hypothalamic gonadotropin-releasing hormone (GnRH) and

pituitary gonadotropin secretion and by impairing gonadal steroidogenesis in both women and men. In the ovary, PRL blocks folliculogenesis and inhibits granulosa cell aromatase activity, leading to

hypoestrogenism and anovulation. PRL also has a luteolytic effect, generating a shortened, or inadequate, luteal phase of the menstrual cycle.

In men, attenuated LH secretion leads to low testosterone levels and

decreased spermatogenesis. These hormonal changes decrease libido

and reduce fertility in patients with hyperprolactinemia.

■ GROWTH HORMONE

Synthesis GH is the most abundant anterior pituitary hormone,

and GH-secreting somatotrope cells constitute up to 50% of the total

2894 PART 12 Endocrinology and Metabolism

anterior pituitary cell population. Mammosomatotrope cells, which

coexpress PRL with GH, can be identified by using double immunostaining techniques. Somatotrope development and GH transcription

are determined by expression of the cell-specific Pit-1 nuclear transcription factor. Five distinct genes encode GH and related proteins.

The pituitary GH gene (hGH-N) produces two alternatively spliced

products that give rise to 22-kDa GH (191 amino acids) and a less

abundant 20-kDa GH molecule with similar biologic activity. Placental syncytiotrophoblast cells express a GH variant (hGH-V) gene; the

related hormone human chorionic somatotropin (HCS) is expressed by

distinct members of the gene cluster.

Secretion GH secretion is controlled by complex hypothalamic and

peripheral factors. GH-releasing hormone (GHRH) is a 44-amino-acid

hypothalamic peptide that stimulates GH synthesis and release. Ghrelin, an octanoylated gastric-derived peptide, and synthetic agonists

of the GHS-R induce GHRH and also directly stimulate GH release.

Somatostatin (somatotropin-release inhibiting factor [SRIF]) is synthesized in the medial preoptic area of the hypothalamus and inhibits GH

secretion. GHRH is secreted in discrete spikes that elicit GH pulses,

whereas SRIF sets basal GH secretory tone. SRIF also is expressed in

many extrahypothalamic tissues, including the central nervous system

(CNS), gastrointestinal tract, and pancreas, where it also acts to inhibit

islet hormone secretion. IGF-1, the peripheral target hormone for

GH, feeds back to inhibit GH; estrogen induces GH, whereas chronic

glucocorticoid excess suppresses GH release, leading to growth delay

in children.

Surface receptors on the somatotrope regulate GH synthesis and

secretion. The GHRH receptor is a G protein–coupled receptor

(GPCR) that signals through the intracellular cyclic AMP pathway

to stimulate somatotrope cell proliferation as well as GH production.

Inactivating mutations of the GHRH receptor cause profound dwarfism. A distinct surface receptor for ghrelin, the gastric-derived GH

secretagogue, is expressed in both the hypothalamus and pituitary.

Somatostatin binds to five distinct receptor subtypes (SST1 to SST5);

SST2 and SST5 subtypes preferentially suppress GH (and TSH) secretion, while SST5 predominantly signals to suppress ACTH secretion.

GH secretion is pulsatile, with highest peak levels occurring at

night, generally correlating with sleep onset. GH secretory rates decline

markedly with age so that hormone levels in middle age are ~15% of

pubertal levels. These changes are paralleled by an age-related decline

in lean muscle mass. GH secretion is also reduced in obese individuals,

although IGF-1 levels may not be suppressed, suggesting a change in

the setpoint for feedback control. Elevated GH levels occur within an

hour of deep sleep onset as well as after exercise, physical stress, and

trauma and during sepsis. Integrated 24-h GH secretion is higher in

women and is also enhanced by estrogen replacement, likely reflective

of increased peripheral GH resistance. Using standard assays, random

GH measurements are undetectable in ~50% of daytime samples

obtained from healthy subjects and are also undetectable (<1 μg/L) in

most obese and elderly subjects. Thus, single random GH measurements do not distinguish patients with adult GH deficiency from those

with GH levels in the normal range.

GH secretion is profoundly influenced by nutritional factors. Using

ultrasensitive GH assays with a sensitivity of 0.002 μg/L, a glucose

load suppresses GH to <0.7 μg/L in women and to <0.07 μg/L in men.

Increased GH pulse frequency and peak amplitudes occur with chronic

malnutrition or prolonged fasting. GH is stimulated by oral ghrelin

receptor agonists, intravenous l-arginine, dopamine, and apomorphine

(a dopamine receptor agonist), as well as by α-adrenergic pathways.

β-Adrenergic blockade induces basal GH and enhances GHRH- and

insulin-evoked GH release.

Action The pattern of GH secretion may affect tissue responses.

The higher GH pulsatility observed in men compared with the relatively continuous basal GH secretion in women may be an important

biologic determinant of linear growth patterns and liver enzyme

induction.

The 70-kDa peripheral GH receptor protein has structural homology

with the cytokine/hematopoietic superfamily. A fragment of the receptor

extracellular domain generates a soluble GH binding protein (GHBP)

that binds to circulating GH. The liver and cartilage express the greatest

number of GH receptors. GH binding to preformed receptor dimers

is followed by internal rotation and subsequent signaling through

the JAK/STAT pathway. Activated STAT proteins translocate to the

nucleus, where they modulate expression of GH-regulated target genes.

GH analogues that bind to the receptor but are incapable of mediating

receptor signaling are potent antagonists of GH action. A GH receptor

antagonist (pegvisomant) is approved for treatment of acromegaly.

GH induces protein synthesis and nitrogen retention and also

impairs glucose tolerance by antagonizing insulin action. GH also

stimulates lipolysis, leading to increased circulating fatty acid levels,

reduced omental fat mass, and enhanced lean body mass. GH promotes

sodium, potassium, and water retention and elevates serum levels of

inorganic phosphate. Linear bone growth occurs as a result of complex

hormonal and growth factor actions, including those of IGF-1. GH

stimulates epiphyseal prechondrocyte differentiation. These precursor

cells produce IGF-1 locally, and their proliferation is also responsive to

the growth factor.

Insulin-Like Growth Factors Although GH exerts direct effects

in target tissues, many of its physiologic effects are mediated indirectly

through IGF-1, a potent growth and differentiation factor. The liver

is the major source of circulating IGF-1. In peripheral tissues, IGF-1

also exerts local paracrine actions that appear to be both dependent on

and independent of GH. Thus, GH administration induces circulating

IGF-1 as well as stimulating local IGF-1 production in multiple tissues.

Both IGF-1 and IGF-2 are bound to high-affinity circulating

IGF-binding proteins (IGFBPs) that regulate IGF availability and bioactivity. Levels of IGFBP3 are GH dependent, and it serves as the major

carrier protein for circulating IGF-1. GH deficiency and malnutrition

usually are associated with low IGFBP3 levels. IGFBP1 and IGFBP2

regulate local tissue IGF action but do not bind appreciable amounts

of circulating IGF-1.

Serum IGF-1 concentrations are profoundly affected by physiologic factors. Levels increase during puberty, peak at 16 years, and

subsequently decline by >80% during the aging process. IGF-1 concentrations are higher in women than in men. Because GH is the

major determinant of hepatic IGF-1 synthesis, abnormalities of GH

synthesis or action (including pituitary failure, GHRH receptor defect,

GH receptor defect, or pharmacologic GH receptor blockade) lead

to reduced IGF-1 levels. Hypocaloric states are associated with GH

resistance; IGF-1 levels are therefore low with cachexia, malnutrition,

and sepsis. In acromegaly, IGF-1 levels are invariably high and reflect a

log-linear relationship with circulating GH concentrations.

IGF-1 PHYSIOLOGY Injected IGF-1 (100 μg/kg) induces hypoglycemia, and lower doses improve insulin sensitivity in patients with severe

insulin resistance and diabetes. In cachectic subjects, IGF-1 infusion

(12 μg/kg per h) enhances nitrogen retention and lowers cholesterol

levels. Longer-term subcutaneous IGF-1 injections enhance protein

synthesis and are anabolic. Although bone formation markers are

induced, bone turnover also may be stimulated by IGF-1. IGF-1 is

approved for use in patients with GH-resistance syndromes.

IGF-1 side effects are dose dependent, and overdose may result

in hypoglycemia, hypotension, fluid retention, temporomandibular

jaw pain, and increased intracranial pressure, all of which are reversible. Retinal damage and avascular femoral head necrosis have been

reported. Chronic excess IGF-1 administration presumably would

result in features of acromegaly.

■ ADRENOCORTICOTROPIC HORMONE

(See also Chap. 386)

Synthesis ACTH-secreting corticotrope cells constitute ~20% of the

pituitary cell population. ACTH (39 amino acids) is derived from the

POMC precursor protein (266 amino acids) that also generates several

2895Physiology of Anterior Pituitary Hormones CHAPTER 378

other peptides, including β-lipotropin, β-endorphin, met-enkephalin,

α-melanocyte-stimulating hormone (α-MSH), and corticotropin-like

intermediate lobe protein (CLIP). The POMC gene is potently suppressed by glucocorticoids and induced by corticotropin-releasing

hormone (CRH), arginine vasopressin (AVP), and proinflammatory

cytokines, including IL-6, as well as leukemia inhibitory factor.

CRH, a 41-amino-acid hypothalamic peptide synthesized in the paraventricular nucleus as well as in higher brain centers, is the predominant stimulator of ACTH synthesis and release. The CRH receptor

is a GPCR that is expressed on the corticotrope and signals to induce

POMC transcription.

Secretion ACTH secretion is pulsatile and exhibits a characteristic

circadian rhythm, peaking at about 6:00 a.m. and reaching a nadir

about midnight. Adrenal glucocorticoid secretion, which is driven by

ACTH, follows a parallel diurnal pattern. ACTH circadian rhythmicity

is determined by variations in secretory pulse amplitude rather than

changes in pulse frequency. Superimposed on this endogenous rhythm,

ACTH levels are increased by physical and psychological stress, exercise, acute illness, and insulin-induced hypoglycemia.

Glucocorticoid-mediated negative regulation of the hypothalamicpituitary-adrenal (HPA) axis occurs as a consequence of both hypothalamic CRH suppression and direct attenuation of pituitary POMC gene

expression and ACTH release. In contrast, loss of cortisol feedback

inhibition, as occurs in primary adrenal failure, results in extremely

high ACTH levels.

Acute inflammatory or septic insults activate the HPA axis through

the integrated actions of proinflammatory cytokines, bacterial toxins,

and neural signals. The overlapping cascade of ACTH-inducing cytokines (tumor necrosis factor [TNF]; IL-1, -2, and -6; and leukemia inhibitory factor) activates hypothalamic CRH and AVP secretion, pituitary

POMC gene expression, and local pituitary paracrine cytokine networks.

The resulting cortisol elevation restrains the inflammatory response

and enables host protection. Concomitantly, cytokine-mediated central

glucocorticoid receptor resistance impairs glucocorticoid suppression

of the HPA. Thus, the neuroendocrine stress response reflects the net

result of highly integrated hypothalamic, intrapituitary, and peripheral

hormone and cytokine signals acting to regulate cortisol secretion.

Action The major function of the HPA axis is to maintain metabolic

homeostasis and mediate the neuroendocrine stress response. ACTH

induces adrenocortical steroidogenesis by sustaining adrenal cell proliferation and function. The receptor for ACTH, designated melanocortin-2 receptor, is a GPCR that induces steroidogenesis by stimulating a

cascade of steroidogenic enzymes (Chap. 386).

■ GONADOTROPINS: FSH AND LH

Synthesis and Secretion Gonadotrope cells constitute ~10% of

anterior pituitary cells and produce two gonadotropin hormones—LH

and FSH. Like TSH and human chorionic gonadotropin, LH and

FSH are glycoprotein hormones that comprise α and β subunits. The

α subunit is common to these glycoprotein hormones; specificity of

hormone function is conferred by the β subunits, which are expressed

by separate genes.

Gonadotropin synthesis and release are dynamically regulated. This

is particularly true in women, in whom rapidly fluctuating gonadal steroid levels vary throughout the menstrual cycle. Hypothalamic GnRH,

a 10-amino-acid peptide, regulates the synthesis and secretion of both

LH and FSH. Brain kisspeptin, a product of the KISS1 gene, regulates

hypothalamic GnRH release. GnRH is secreted in discrete pulses every

60–120 min, and the pulses in turn elicit LH and FSH pulses (Fig. 378-3).

The pulsatile mode of GnRH input is essential to its action; pulses

prime gonadotrope responsiveness, whereas continuous GnRH exposure induces desensitization. Based on this phenomenon, long-acting

GnRH agonists are used to suppress gonadotropin levels in children

with precocious puberty and in men with prostate cancer (Chap. 87)

and are used in some ovulation-induction protocols to reduce levels

of endogenous gonadotropins (Chap. 392). Estrogens act at both the

hypothalamus and the pituitary to modulate gonadotropin secretion.

Chronic estrogen exposure is inhibitory, whereas rising estrogen levels, as occur during the preovulatory surge, exert positive feedback to

increase gonadotropin pulse frequency and amplitude. Progesterone

slows GnRH pulse frequency but enhances gonadotropin responses

to GnRH. Testosterone feedback in men also occurs at the hypothalamic and pituitary levels and is mediated in part by its conversion to

estrogens.

Although GnRH is the main regulator of LH and FSH secretion,

FSH synthesis is also under distinct control by the gonadal peptides

inhibin and activin, members of the transforming growth factor β

(TGF-β) family. Inhibin selectively suppresses FSH, whereas activin

stimulates FSH synthesis (Chap. 392).

Action The gonadotropin hormones interact with their respective

GPCRs expressed in the ovary and testis, evoking germ cell development and maturation and steroid hormone biosynthesis. In women,

FSH regulates ovarian follicle development and stimulates ovarian

estrogen production. LH mediates ovulation and maintenance of the

corpus luteum. In men, LH induces Leydig cell testosterone synthesis

and secretion, and FSH stimulates seminiferous tubule development

and regulates spermatogenesis.

■ THYROID-STIMULATING HORMONE

Synthesis and Secretion TSH-secreting thyrotrope cells constitute 5% of the anterior pituitary cell population. TSH shares a common

α subunit with LH and FSH but contains a specific TSH β subunit.

TRH is a hypothalamic tripeptide (pyroglutamyl histidylprolinamide)

that acts through a pituitary GPCR to stimulate TSH synthesis and

secretion; it also stimulates the lactotrope cell to secrete PRL. TSH

secretion is stimulated by TRH, whereas thyroid hormones, dopamine,

somatostatin, and glucocorticoids suppress TSH by overriding TRH

induction.

Thyrotrope cell proliferation and TSH secretion are both induced

when negative feedback inhibition by thyroid hormones is removed.

Thus, thyroid damage (including surgical thyroidectomy), radiation-induced hypothyroidism, chronic thyroiditis, and prolonged

goitrogen exposure are associated with increased TSH levels.

Long-standing untreated hypothyroidism can lead to elevated TSH levels, which may be associated with thyrotrope hyperplasia and pituitary

enlargement and may sometimes be evident on magnetic resonance

imaging.

Action TSH is secreted in pulses, although the excursions are

modest in comparison to other pituitary hormones because of the low

amplitude of the pulses and the relatively long half-life of TSH. Consequently, single determinations of TSH suffice to precisely assess its

circulating levels. TSH binds to a GPCR on thyroid follicular cells to

stimulate thyroid hormone synthesis and release (Chap. 382).

■ FURTHER READING

Bernard V et al: Prolactin: A pleiotropic factor in health and disease.

Nat Rev Endocrinol 15:356, 2019.

Cheung LYM et al: Single-cell RNA sequencing reveals novel markers

of male pituitary stem cells and hormone-producing cell types. Endocrinology 159:3910, 2018.

Das N, Kumar TR: Molecular regulation of follicle-stimulating hormone synthesis, secretion and action. J Mol Endocrinol 60:R131,

2018.

Langlais D et al: Adult pituitary cell maintenance: Lineage-specific

contribution of self-duplication. Mol Endocrinol 27:1103, 2013.

Le Tissier P et al: The process of anterior pituitary hormone pulse

generation. Endocrinology 159:3524, 2018.

Murray PG et al: 60 years of neuroendocrinology: The hypothalamoGH axis: The past 60 years. J Endocrinol 226:T123, 2015.

Ranke MB, Wit JM: Growth hormone: Past, present and future.

Nat Rev Endocrinol 14:285, 2018.